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Journal articles on the topic 'L-Methadon'

Author: Grafiati

Published: 4 June 2021

Last updated: 1 February 2022

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1

Friesen, Claudia. "D,L-Methadon erhöht den zytotoxischen Effekt konventioneller Krebstherapien." Deutsche Zeitschrift für Onkologie 49, no. 02 (June 2017): 61–67. http://dx.doi.org/10.1055/s-0043-110160.

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ZusammenfassungResistenzen gegenüber konventionellen Behandlungsmethoden limitieren den Erfolg in der Krebstherapie. Dies fordert, neue Therapiestrategien zu entwickeln, um den therapeutischen Erfolg zu verbessern. Krebszellen exprimieren auf ihrer Zelloberfläche sehr stark Opioidrezeptoren. Dies ermöglicht Opioiden, an die Krebszelle zu binden.Methadon, das an Opioidrezeptoren bindet und in der Schmerztherapie bei Tumorpatienten eingesetzt wird, hat in vitro und im Mausmodell in vivo gezeigt, dass Chemotherapeutika in ihrer zytotoxischen Wirkung verstärkt werden können. Über die Aktivierung des Opioidrezeptors und die Herunterregulation von zyklischem Adenosinmonophosphat (cAMP) kann D,L-Methadon Apoptose-Signalwege aktivieren und antiapoptotische Moleküle, die zur Therapieresistenz führen können, blockieren. Des Weiteren kann D,L-Methadon zur einer stärkeren Aufnahme des Chemotherapeutikum in der Tumorzelle führen. Hierbei kommt es auf die Expression der Opioidrezeptoren auf der Oberfläche der Tumorzellen an. Bei einer starken Expression kann D,L-Methadon sogar allein den Zelltod in der Tumorzelle auslösen. Bei einer moderaten Expression verstärkt D,L-Methadon konventionelle Therapien in ihrer zytotoxischen Wirkung. Gesundes Gewebe, das wenig oder keine Opioidrezeptoren exprimiert, wird von der zytotoxischen Verstärkung von D,L-Methadon verschont. In einer retrospektiven klinischen Studie zur Behandlung von Gliomen wurde gezeigt, dass D,L-Methadon ohne erhebliche oder toxische Nebenwirkungen zusätzlich bei der Behandlung von Gliomen eingesetzt werden kann.

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2

Friese, Klaus. "Methadon-Hype und der verunsicherte Tumorpatient." Deutsche Zeitschrift für Onkologie 49, no. 03 (September 2017): 102. http://dx.doi.org/10.1055/s-0043-113537.

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In dieser Zeitschriftwurde in der letzten Ausgabe (2/2017) von Frau Dr. rer. nat. Claudia Friesen über ihre Beobachtung beim Einsatz von D,L-Methadon berichtet (D,L-Methadon erhöht den zytotoxischen Effekt konventioneller Krebstherapie). Dabei beschreibt die Autorin z.T. ältere Laborversuche bezüglich der Apoptose beim Einsatz von Methadon in Kombination mit Chemotherapie sowie den retrospektiven Einsatz, z. B. bei 27 Gliompatienten. Diese Mitteilung hat zu einer massiven Verunsicherung und unbegründeter Hoffnung bei Tumorpatienten durch die Medien geführt.

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3

Lehmann, K., M. Abu-Shibika, and Gabriele Horrichs-Haermeyer. "Postoperative Schmerztherapie mit l-Methadon und Metamizol." AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie 25, no. 02 (April 1990): 152–59. http://dx.doi.org/10.1055/s-2007-1001039.

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4

Banzer, K., B. Erbas, G. Koller, M. Backmund, and M. Soyka. "Substitutionsbehandlung Drogenabhängiger." Nervenheilkunde 25, no. 04 (2006): 286–94. http://dx.doi.org/10.1055/s-0038-1626467.

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ZusammenfassungDie Substitutionsbehandlung Drogenabhängiger ist eine der realistischen therapeutischen Optionen. Ihre Umsetzung scheitert häufig an Unkenntnis der rechtlichen Grundlagen und der praktischen Durchführung, die dargestellt werden. Mittlerweile stehen mit Methadon, L-Methadon und Buprenorphin verschiedene Substitutionsmittel zur Verfügung mit möglicherweise differenziellen Indikationskriterien. Wichtig ist auch die Mitbehandlung körperlicher Begleitererkrankungen, speziell HIV und Hepatitis. Aktuelle Indikationsempfehlungen werden berichtet

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5

Kiefer, I., K. Becker, G. Oechtering, and M. Alef. "Der Einfluss etablierter Anästhesieprotokolle auf die Sauerstoff-versorgung des Hirngewebes beim Hund." Tierärztliche Praxis Ausgabe K: Kleintiere / Heimtiere 36, no. 03 (2008): 157–68. http://dx.doi.org/10.1055/s-0038-1622672.

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Zusammenfassung:Gegenstand und Ziel: Die Nah-infrarot-Spektroskopie (NIRS) überwacht kontinuierlich die zerebrale Sauerstoffund Blutversorgung und so die Grundlagen einer ungestörten neurologischen Funktion. Ziel der Studie ist die Darstellung der Auswirkungen verschiedener Anästhesieprotokolle auf die zerebrale Sauerstoffversorgung beim Hund. Material und Methoden: In einer experimentellen Studie wurden die Veränderungen der zerebralen Oxygenierung und des Redoxzustandes von Cytochrom a/a3 nach verschiedenen zur intravenösen Narkoseeinleitung etablierten Protokollen (Acepromazin & l-Methadon [AM], Diazepam & l-Methadon [DM], Medetomidin & l-Methadon [MM], Propofol [P]) untersucht und der Zusammenhang mit pulmonalem Gaswechsel und Herz-Kreislauf-Funktion betrachtet. Ergebnisse: Die Methode ist geeignet, die durch eine Narkoseeinleitung beim Hund verursachten Veränderungen der zerebralen Oxygenierung aufzuzeigen. Ausgehend von einer regionalen zerebralen Sauerstoffsättigung von etwa 65% (n = 109, STD 7%) am wachen Hund bestehen eine Minute nach Einleitung signifikante Gruppenunterschiede. In der Propofol-Gruppe steigt die regionale zerebrale Sauerstoffsättigung um etwa 8%. In allen anderen Gruppen fällt sie, nach AM um 5%, nach DM um bis zu 10%, nach MM um maximal 20%. Der zerebrale Gesamthämoglobingehalt zeigt keine Gruppenunterschiede. Die Narkoseeinleitung hat keinen Effekt auf den Redoxzustand von Cytochrom a/a3. Korrelationen der zerebralen Oxygenierung mit arteriellem Sauerstoffstatus und Kohlendioxidpartialdruck bestehen. Schlussfolgerungen: Die NIRS eröffnet erstmals die Möglichkeit, die Auswirkungen von in der klinischen Routine eingeführten Verfahren auf die zerebrale Oxygenierung darzustellen. Eine Abnahme der regionalen zerebralen Sauerstoffsättigung um etwa 20% (MM) über die gesamte Messdauer scheint von klinischer Relevanz und wird als Indiz einer kritischen zerebralen Sauerstoffversorgung beurteilt. Die anästhetikabedingte Atemdepression hat einen entscheidenden Einfluss auf den vaskulären zerebralen Sauerstoffstatus. Klinische Relevanz: Atemdepressive Narkoseprotokolle können beim spontan atmenden Hund zu einer kritischen zerebralen Sauerstoffversorgung führen.

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6

Emrich, Oliver. "D,L-Methadon — eine neue Wunderwaffe in der Tumor(Schmerz)-Therapie?" Schmerzmedizin 33, no. 4 (July 2017): 47–48. http://dx.doi.org/10.1007/s00940-017-0608-2.

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7

Petrat, C., M. Steiner, U. Wedding, and W. Meißner. "Opiatrotation auf L-Methadon (L-Polamidon) bei Opiatgewöhnung und schwer beherschbaren Schmerzen – eine therapiebegleitende Analyse." Zeitschrift für Palliativmedizin 17, no. 05 (December 13, 2016): 1–59. http://dx.doi.org/10.1055/s-0036-1594139.

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8

Verthein, Uwe, Jens Reimer, Rainer Ullmann, and Christian Haasen. "Psychische Befindlichkeit in der Substitutionsbehandlung mit Levomethadon und d,l-Methadon – eine doppel-blinde randomisierte Cross-over-Studie." SUCHT 53, no. 1 (January 2007): 32–41. http://dx.doi.org/10.1024/2007.01.05.

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<span class="fett">Fragestellung:</span> Ziel der Studie war zu zeigen, ob sich bei einem Wechsel der in der Substitutionsbehandlung Opiatabhängiger eingesetzten Substanzen Levomethadon und d,l-Methadon das psychische Befinden und das Verlangen nach Drogen ändern. </p><p> <span class="fett">Methodik:</span> Es wurde eine stratifizierte, randomisierte 2×2-Cross-over-Studie doppelblind über 8 Wochen durchgeführt. Zu Beginn und nach 4 Wochen wurde die Studienmedikation umgestellt. </p><p> <span class="fett">Untersuchungsgruppe:</span> 75 Patienten, die sich seit mindestens einem Jahr in Substitutionsbehandlung befanden, wurden in die Studie eingeschlossen. Von 68 Patienten liegen vollständige Ergebnisse vor. </p><p> <span class="fett">Ergebnisse:</span> In keinem der Merkmale – psychische Befindlichkeit, depressive Verstimmungen, Ängstlichkeit, Drogenverlangen und Drogenkonsum – konnte ein mit der Umstellung des Substitutionsmittels zusammenhängender Effekt beobachtet werden. Kurzfristige, vorübergehende Befindlichkeitsschwankungen regulierten sich wieder auf einen Zustand, der vor Cross-over zu beobachten war. </p><p> <span class="fett">Schlussfolgerungen:</span> Levomethadon und d,l-Methadon können im entsprechenden Dosisverhältnis gleichberechtigt eingesetzt werden.

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9

Möller, Michael, Christoph Althaus, and Rainer Sundmacher. "Beidseitige Candida-Endophthalmitis zweier i.v.-drogenabhängiger Patienten unter oraler L-Methadon-Substitution." Klinische Monatsblätter für Augenheilkunde 211, no. 07 (July 1997): 53–56. http://dx.doi.org/10.1055/s-2008-1035095.

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10

Becker, K., C. Haarstrick, G. Oechtering, M. Alef, and I. Kiefer. "Auswirkung einer Neuroleptanalgesie mit Acepromazin auf die Durchblutung der Niere beim Hund." Tierärztliche Praxis Ausgabe K: Kleintiere / Heimtiere 39, no. 03 (2011): 154–62. http://dx.doi.org/10.1055/s-0038-1623573.

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Zusammenfassung Gegenstand und Ziel: Das postanästhetische Nierenversagen ist eine gefürchtete Komplikation einer Narkose. Nicht wenige Patienten leiden an einer kompensierten Niereninsuffizienz, die durch zusätzliche Belastungen wie Operation und Narkose in eine akute Niereninsuffizienz übergehen kann. Ziel der Studie war, die Auswirkung einer Neuroleptanalgesie mit Acepromazin auf sonographisch erfassbare Durchblutungsparameter zu untersuchen. Material und Methoden: Bei 19 klinisch gesunden Hunden der Rassen Foxhound und Beagle erfolgte unter Acepromazin/l-Methadon-Narkose (0,1 mg/kg KM Acepromazin; 0,5 mg/kg KM l-Methadon) eine sonographische Untersuchung der linken Niere. Alle 5 Minuten wurden Resistance-Index und Pulsatilitätsindex bestimmt und digital aufgezeichnet, ebenso der invasiv gemessene Blutdruck. Ergebnisse: Fünf Minuten nach Narkoseeinleitung stieg der mittlere arterielle Blutdruck an, fiel aber bereits nach 10 Minuten wieder auf den Ausgangswert zurück und änderte sich im weiteren Verlauf nur noch unwesentlich. Resistance-Index und Pulsatilitätsindex verhielten sich vergleichbar: Nach einem geringgradigen Abfall nach 5 Minuten stiegen die Werte beider Parameter signifikant an. Dieser Anstieg war bis 15 Minuten nach Narkoseeinleitung sehr stark und verlief dann bis zum Ende der Untersuchung nach 30 Minuten deutlich flacher. Die Werte entsprachen denen einer Gefäßstenose. Schlussfolgerung und klinische Relevanz: Aufgrund der erhaltenen Messwerte wird davon abgeraten, diese Form der Anästhesie beim nierenkranken Hund einzusetzen, wenngleich sich die Ergebnisse dieser experimentellen Studie nicht auf den klinischen Patienten übertragen lassen.

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11

Siedentopf, J. P., M. Nagel, M. Eßer, S. Casteleyn, and J. Dudenhausen. "Erfahrungen mit der Buprenorphineinstellung und anschließenden Dosisreduktion im Vergleich zu L-Methadon bei schwangeren Opiatabhängigen." Geburtshilfe und Frauenheilkunde 64, no. 07 (July 7, 2004): 711–18. http://dx.doi.org/10.1055/s-2004-821005.

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12

Drasch, G., D. Quitterer, G. Roider, and L. von Meyer. "Der stereoselektive Nachweis von l - und d -Methadon in Blutproben von lebenden und verstorbenen Drogenabhängigen." Rechtsmedizin 10, no. 5 (October 27, 2000): 170–75. http://dx.doi.org/10.1007/s001940000067.

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13

Holtman, Joseph R., and Elzbieta P. Wala. "Characterization of the Antinociceptive and Pronociceptive Effects of Methadone in Rats." Anesthesiology 106, no. 3 (March 1, 2007): 563–71. http://dx.doi.org/10.1097/00000542-200703000-00022.

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Background Recently, it has been appreciated that in addition to their antinociceptive properties, opioid analgesics also can enhance pain sensitivity (opioid-induced hyperalgesia [OIH]). OIH may enhance preexisting pain and contribute to dose escalation, tolerance, and misuse/abuse of opioids. Better information is needed to determine which opioid or opioid combinations may be least likely to produce OIH and therefore possibly represent better choices for pain management. Herein the authors have examined the hyperalgesic and antinociceptive properties of racemic methadone and its enantiomers alone and in combination with morphine in rats. Methadone is of particular interest because it possesses both micro-receptor agonist and N-methyl-d-aspartate receptor antagonist activities. Methods The antinociceptive and hyperalgesic properties of d,l-methadone, l-methadone, and d-methadone were characterized by dose and sex using the thermal tail-flick test (high and low intensity). The responses to l- and d-methadone combinations with morphine were also determined with this model. Results Antinociceptive and hyperalgesic effects of d,l-methadone were demonstrated. These effects were related to dose but not to sex. The degree of hyperalgesia was greater with l-methadone compared with d,l-methadone. In contrast, d-methadone (N-methyl-d-aspartate antagonist) did not produce hyperalgesia. Furthermore, d-methadone blocked morphine hyperalgesia, enhanced antinociception, and abolished sex-related differences. This seems to be the result of antagonistic activity of d-methadone at the N-methyl-d-aspartate receptor. Conclusion The current findings with methadone are supportive of previous findings implicating mu-opioid and N-methyl-d-aspartate receptor mechanisms in OIH. Better understanding of OIH may help in choosing the most appropriate opioids for use in the treatment of pain.

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Allen, Jeffrey W., Kjersti A. Horais, Nicolle A. Tozier, and Tony L. Yaksh. "Opiate Pharmacology of Intrathecal Granulomas." Anesthesiology 105, no. 3 (September 1, 2006): 590–98. http://dx.doi.org/10.1097/00000542-200609000-00025.

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Background Chronic intrathecal morphine infusion produces intradural granulomas. The authors examined a variety of opioids infused intrathecal for analgesic activity and toxicity. Methods Two sets of experiments were undertaken in dogs with chronic intrathecal catheters: (1) Six-hour intrathecal infusions were used to determine the full analgesic dose and the maximum tolerated dose. (2) To establish toxicity, the maximum tolerated dose was given for up to 28 days by continuous intrathecal infusion. Drugs examined were morphine sulfate, hydromorphone, D/L-methadone, L-methadone, D-methadone, fentanyl, [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), naloxone, or saline. RESULTS ANALGESIA AND TOLERABILITY: Six-hour intrathecal infusion of agonists resulted in a time-dependent increase in thermal escape latency. At higher concentrations, dose-limiting motor dysfunction and sedation occurred, and hypersensitivity occurred. The concentrations, in mg/ml, for full analgesic dose/maximum tolerated dose were as follows: morphine, 0.9/12.0; hydromorphone, 1.0/3.0; D/L-methadone, 2.8/3; L-methadone, 1.0/> 1.0; fentanyl, 0.3/2.0; DAMGO, 0.1/> 2.0; D-methadone, > 1/> 1; naloxone, > 10/> 10. SPINAL PATHOLOGY: Chronic intrathecal infusion of the maximum tolerated dose revealed 100% intradural granuloma formation after morphine, hydromorphone, L-methadone, and naloxone. DAMGO induced a mass in only a single animal (one of three). D/L- and D-methadone produced intradural granulomas but were also associated with parenchymal necrosis. Saline and fentanyl animals displayed no granulomas. Conclusions Intrathecal opiate-induced granulomas are not strictly dependent on opioid receptor activation. Therefore, opiates at equianalgesic doses present different risks for granuloma formation. Importantly, D/L- and D-methadone also resulted in parenchymal necrosis, an affect associated with the N-methyl-D-aspartate antagonist action of the D-isomer.

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15

Wolff, K., A. W. Hay, and D. Raistrick. "Plasma Methadone Measurements and Their Role in Methadone Detoxification Programs." Clinical Chemistry 38, no. 3 (March 1, 1992): 420–25. http://dx.doi.org/10.1093/clinchem/38.3.420.

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Abstract We monitored eight patients who were receiving a decreasing dose of methadone for treatment for opioid addiction (detoxification). Patients with plasma concentrations of methadone less than 0.05 mg/L experienced withdrawal symptoms, relapsed, and re-abused illicit drugs. Four patients took extra methadone (illicitly obtained) during detoxification. None of the eight patients in our study were successfully weaned off methadone: all left the methadone detoxification program before the completion of treatment. Two patients subsequently returned to a fixed methadone program elsewhere, and four relapsed and returned to illicit drug misuse. Plasma measurements may help clinicians assess patients during methadone detoxification.

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George, S., S. Parmar, C. Meadway, and R. A. Braithwaite. "Application and validation of a urinary methadone metabolite (EDDP) immunoassay to monitor methadone compliance." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 37, no. 3 (May 1, 2000): 350–54. http://dx.doi.org/10.1258/0004563001899267.

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A total of 1381 urine specimens were screened using a Microgenics CEDIA urinary primary methadone metabolite (2-ethylidene-1,5-dimethyl-3,3- diphenylpyrrolidine; EDDP) immunoassay (cut-off calibrator concentration of 100 µg/L) in combination with a Dade Behring EMIT urinary methadone immunoassay (cut-off calibrator concentration of 300 µg/L). Of these, 642 (46%) were found to be positive using the EDDP assay but only 541 (39%) were found to be positive by the methadone assay. Out of the 108 specimens which were EDDP-positive but negative by the methadone assay, 47 (7%) could not be confirmed as positive using the routine in-house method of gas chromatography incorporating nitrogen-specific detection. Of these 47 results, 38 were re-screened using a more sensitive gas chromatography-mass spectrometry (GC-MS) technique, which demonstrated the presence of EDDP in every case. There was insufficient specimen to analyse the remaining nine samples. There were seven specimens which gave negative results by the EDDP and GC-MS assays but which had methadone concentrations ranging from 4000 to 37 500 µg/L. These were therefore presumed to be 'spiked' with methadone, i.e. to have had methadone added to the specimen to yield positive screening results and simulate compliance. It is concluded that the Microgenics CEDIA EDDP assay is a sensitive and reliable technique to determine the compliance of subjects prescribed methadone for opiate detoxification and maintenance.

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17

Wolff, Kim, Marion Sanderson, Alastalr W. Hay, and Duncan Raistrick. "Methadone concentrations in plasma and their relationship to drug dosage." Clinical Chemistry 37, no. 2 (February 1, 1991): 205–9. http://dx.doi.org/10.1093/clinchem/37.2.205.

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Abstract We have developed a sensitive HPLC method for measuring methadone in plasma and have used it to establish that there is a linear relationship between plasma concentration and methadone dose over the range of 3-100 mg of methadone per day in a group of 31 addicts. We found a good correlation between dose and plasma concentration (r = 0.89), with the plasma methadone concentration increasing by 0.263 mg/L for every milligram of methadone consumed per kilogram of body weight. Five patients had unexpected high or low concentrations; this finding is discussed.

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18

Wolff, K., A. Hay, and D. Raistrick. "High-dose methadone and the need for drug measurements in plasma." Clinical Chemistry 37, no. 9 (September 1, 1991): 1651–54. http://dx.doi.org/10.1093/clinchem/37.9.1651.

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Abstract We report a case of high-dose methadone prescribed to a heroin addict for pain control. The patient was prescribed methadone during convalescence from surgery and subsequently for maintenance treatment. Dosing was started at 360 mg of methadone per day and reduced over 12 days to an 80 mg/day maintenance dose. Although the patient was drowsy on the initial dose, his recovery was uneventful. However, there were complaints of pain and withdrawal discomfort when the plasma concentration decreased to less than 1 mg/L. Measurements of methadone in plasma were helpful for monitoring the recovery of this patient after surgery and are likely to prove useful in similar cases.

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19

Perez-Alvarez, Sergio, Maria E. Solesio, Maria D. Cuenca-Lopez, Raquel M. Melero-Fernández de Mera, Carlos Villalobos, Hanna Kmita, Maria F. Galindo, and Joaquin Jordán. "Pharmacological Characterization of the Mechanisms Involved in Delayed Calcium Deregulation in SH-SY5Y Cells Challenged with Methadone." International Journal of Cell Biology 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/642482.

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Previously, we have shown that SH-SY5Y cells exposed to high concentrations of methadone died due to a necrotic-like cell death mechanism related to delayed calcium deregulation (DCD). In this study, we show that, in terms of their Ca2+responses to 0.5 mM methadone, SH-SY5Y cells can be pooled into four different groups. In a broad pharmacological survey, the relevance of different Ca2+-related mechanisms on methadone-induced DCD was investigated including extracellular calcium, L-type Ca2+channels,μ-opioid receptor, mitochondrial inner membrane potential, mitochondrial ATP synthesis, mitochondrial Ca2+/2Na+-exchanger, reactive oxygen species, and mitochondrial permeability transition. Only those compounds targeting mitochondria such as oligomycin, FCCP, CGP 37157, and cyclosporine A were able to amend methadone-induced Ca2+dyshomeostasis suggesting that methadone induces DCD by modulating the ability of mitochondria to handle Ca2+. Consistently, mitochondria became dramatically shorter and rounder in the presence of methadone. Furthermore, analysis of oxygen uptake by isolated rat liver mitochondria suggested that methadone affected mitochondrial Ca2+uptake in a respiratory substrate-dependent way. We conclude that methadone causes failure of intracellular Ca2+homeostasis, and this effect is associated with morphological and functional changes of mitochondria. Likely, this mechanism contributes to degenerative side effects associated with methadone treatment.

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van Donge, T., S. Samiee-Zafarghandy, M. Pfister, G. Koch, M. Kalani, A. Bordbar, and J. van den Anker. "O06 Methadone dosing strategies in preterm neonates can be simplified." Archives of Disease in Childhood 104, no. 6 (May 17, 2019): e3.1-e3. http://dx.doi.org/10.1136/archdischild-2019-esdppp.6.

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AimsA dramatic increase in newborn infants with neonatal abstinence syndrome has been observed and these neonates are frequently treated with complex methadone dosing schemes to control their withdrawal symptoms. Despite its abundant use, hardly any data on the pharmacokinetics of methadone is available in preterm neonates. Therefore we investigated developmental pharmacokinetics of methadone and evaluated current dosing strategies and possible simplification in this vulnerable population.MethodsA single center open-label prospective study was performed to collect pharmacokinetic data after a single oral dose of methadone in preterm neonates. A population pharmacokinetic model was built to characterize developmental pharmacokinetics of methadone and to assess the effects of weight and age on clearance and volume of distribution. In addition, simulation techniques were applied to evaluate reported dosing scenarios, investigate methadone exposure levels and examine the feasibility of simplified dosing recommendations.ResultsIn total, 121 methadone concentrations were collected from 31 preterm neonates. The median weight and gestational age amounted 1.6 kg and 32 weeks, respectively. A one-compartment model with first order absorption and elimination kinetics best described the data for (R)- and (S)-methadone. Clearance was observed to be higher for the (R)-enantiomer as compared to the (S)-enantiomer (0.244 versus 0.167 L/h). Target exposures, based on simulations, can be maintained with a simplified dosing strategy during the first four days of treatment. It is therefore questionable if there is a need for the currently used more extended dosing regimen of methadone in neonates.conclusionsThis clinical investigation demonstrates that the clearance of methadone increases with advancing gestational age and higher clearance values and volumes of distribution can be observed for (R)-methadone as compared to (S)-methadone in preterm neonates. Simulations that account for developmental pharmacokinetics indicate that a simplified methadone dosing strategy can maintain target exposure to control withdrawal symptoms in preterm neonates.Disclosure(s)Nothing to disclose

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Verthein, Uwe, Rainer Ullmann, Anke Lachmann, Andreas Düring, Barbara Koch, Hans-Günter Meyer-Thompson, Rolf Schmidt, Jens Reimer, and Christian Haasen. "The effects of racemic d,l-methadone and l-methadone in substituted patients—a randomized controlled study." Drug and Alcohol Dependence 80, no. 2 (November 2005): 267–71. http://dx.doi.org/10.1016/j.drugalcdep.2005.04.007.

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22

D’Hotman, Daniel, Jonathan Pugh, and Thomas Douglas. "The Case against Forced Methadone Detox in the US Prisons." Public Health Ethics 12, no. 1 (November 19, 2016): 89–93. http://dx.doi.org/10.1093/phe/phw040.

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Abstract Methadone maintenance therapy is a cost-effective, evidence-based treatment for heroin dependence. In the USA, a majority of heroin-dependent offenders are forced to detox from methadone when incarcerated. Recent research published in The Lancet has demonstrated the negative health and economic outcomes associated with such policies (Rich, J. D., McKenzie, M., Larney, S., Wong, J. B., Tran, L., Clarke, J. et al. (2015). Methadone Continuation Versus Forced Withdrawal on Incarceration in a Combined US Prison and Jail: A Randomised, Open Label Trial. The Lancet, 386, 350–359). This novel evidence raises questions as to the justification for current policies of forced detox in American prisons. Opponents of methadone provision in prisons might offer arguments from retributivism, resource allocation and curative effectiveness to justify their position. This article contends that these arguments do not stand up to ethical scrutiny. In light of this, we hold that American policymakers should reform criminal justice policies to allow the initiation and continuation of methadone treatment in correctional settings. This would be consistent with both international recommendations and the example set by a number of other Western countries.

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Banger, M., and T. Finkbeiner. "20 DETECTION OF METHADONE INTAKE BY IMMUNO-ANALYSIS OF URINE AFTER CHANGING FROM L-METHADONE TO D/I-METHADONE DURING METHADONE-MAINTENANCE THERAPY." Therapeutic Drug Monitoring 17, no. 4 (August 1995): 388. http://dx.doi.org/10.1097/00007691-199508000-00032.

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de Vos, Jan W., Jan G. R. Ufkes, Charles D. Kaplan, Marcus Tursch, Joachim K. A. Krause, Henk van Wilgenburg, Barry G. Woodcock, and A. Horst Staib. "L-Methadone and D,L-Methadonein Methadone Maintenance Treatment: A Comparison of Therapeutic Effectiveness and Plasma Concentrations." European Addiction Research 4, no. 3 (1998): 134–41. http://dx.doi.org/10.1159/000018936.

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Wilson, J. F., J. Williams, G. Walker, P. A. Toseland, B. L. Smith, A. Richens, and D. Burnett. "Performance of techniques used to detect drugs of abuse in urine: study based on external quality assessment." Clinical Chemistry 37, no. 3 (March 1, 1991): 442–47. http://dx.doi.org/10.1093/clinchem/37.3.442.

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Abstract Twenty-five samples of lyophilized urine from the U.K. External Quality Assessment Scheme for Drugs of Abuse were analyzed by an average of 95 laboratories between April 1987 and December 1989. Samples contained mixtures of analytes and included replicated concentrations of morphine, methadone, amphetamine, and cocaine at 0, 1, 2, and 5 mg/L and of benzoylecgonine at 0, 0.4, 1, 2, and 4 mg/L. Some chromatographic techniques were inadequate for detecting morphine, amphetamine, cocaine, and benzoylecgonine at the lower concentrations of analytes studied: gas-liquid chromatography was least sensitive for morphine; in-house thin-layer chromatography (TLC) was least sensitive for the other analytes. Few significant differences in specificity were detected between techniques, although significant interference from structurally related compounds was demonstrated in assays of morphine, methadone, and amphetamine. Exceptions were the Boehringer (BCL) test for opiates and TLC applied to amphetamine and benzoylecgonine, which demonstrated considerable lack of specificity.

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Meini, Milo, Marco Moncini, Laura Daini, Tania Giarratana, Daniela Scaramelli, Silvio Chericoni, Fabio Stefanelli, and Paola Rucci. "Relationship between plasma concentrations of the l-enantiomer of methadone and response to methadone maintenance treatment." European Journal of Pharmacology 760 (August 2015): 1–6. http://dx.doi.org/10.1016/j.ejphar.2015.03.081.

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Kramer, S., I. Nolte, and W. Jochle. "Clinical comparison of medetomidine with xylazine/l-methadone in dogs." Veterinary Record 138, no. 6 (February 10, 1996): 128–33. http://dx.doi.org/10.1136/vr.138.6.128.

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Khoubnasabjafari, Maryam, Khalil Ansarin, Vahid Jouyban-Gharamaleki, Vahid Panahi-Azar, Ali Shayanfar, Laya Mohammadzadeh, and Abolghasem Jouyban. "Extraction and Analysis of Methadone in Exhaled Breath Condensate Using a Validated LC-UV Method." Journal of Pharmacy & Pharmaceutical Sciences 18, no. 2 (June 5, 2015): 207. http://dx.doi.org/10.18433/j3wk65.

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Purpose. A combined microextraction and separation method is presented for the determination of methadone in exhaled breath condensate (EBC) which is a promising non-invasive biological component for monitoring drug concentrations. Methods. In this work, dispersive liquid–liquid microextraction (DLLME) and ultrasonic liquid–liquid microextraction (ULLME) procedure coupled with a validated liquid chromatography method were used for analysis of methadone in EBC collected using an in-house cold trap setup. The method has been validated according to the FDA guidelines using EBC-spiked samples and tested on a number of EBC samples collected from patients. Results. The best DLLME conditions involved the use of a disperser solvent of methanol (1 mL), extraction solvent of chloroform (200 mL), EBC sample pH of 10.0 and centrifugation at 6000 rpm for 5 minutes. The conditions for ULLME were 150 mL of chloroform and the samples were sonicated for 4 minutes. The method was validated over the concentration range of 0.5–10 mg/L-1 in EBC. Inter- and intra-day precision and accuracy were less than 5 % where the acceptable levels are less than 20%. Furthermore, the validated method was successfully applied for the determination of methadone in patients’ EBC samples. Conclusions. The outcomes indicate that the developed LC-UV combined with DLLME and/or ULLME extraction methods can be employed for the extraction and separation of methadone in EBC samples. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Scherhaum, N., T. Finkbeiner, K. Leifert, and M. Gastpar. "The Efficacy of L-methadone and Racemic Methadone in Substitution Treatment for Opiate Addicts - A Double-blind Comparison." Pharmacopsychiatry 29, no. 06 (November 1996): 212–15. http://dx.doi.org/10.1055/s-2007-979573.

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Farmer, Charles C., and Monica Agarwal. "Endocrinopathies Associated With High Dose Methadone." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A130. http://dx.doi.org/10.1210/jendso/bvab048.262.

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Abstract Introduction: The opioid epidemic is a public health crisis and clinicians should be aware of the many under-recognized endocrinopathies associated with opioids. Herein, we present a case that exemplifies the endocrine-related adverse effects of methadone therapy. Clinical Case: A 43-year-old Caucasian female with chronic back pain with opioid dependence, high dose methadone use (195 mg daily), and diabetes presented with refractory hypoglycemia. She was diagnosed with ketone prone diabetes eight months prior. She had since been weaned off insulin and her most recent HbA1c was 4.2%. During this time, she had an intentional weight loss of 60 pounds. On examination, she had bilateral lower extremity pitting edema with scaly plaques on the extremities. Laboratory tests showed C-peptide of 0.8 (0.9–7.1 ng/mL), insulin level of < 2 (3–25 mcIntUnits/mL), proinsulin of 4.6 (<18.8 pMol/L) with concurrent glucose of 48 mg/dl. She failed the ACTH stimulation test with 60 minute cortisol of 16.8 mcg/dL and was started on prednisone for adrenal insufficiency (AI). The pituitary and adrenal were normal on imaging. Her albumin was 1.5 (3.7–5.5 gm/dL) and she had vitamin and micronutrient deficiencies including copper, zinc, thiamine, selenium, and vitamin A. The insulin antibody test, paraneoplastic panel, celiac panel, A1 antitrypsin test, EGD, and colonoscopy were all non-revealing. A liver biopsy showed glycogenic hepatopathy. She improved clinically after prednisone initiation and treatment of malnutrition. The hypoglycemia improved but did not resolve as she refused to reduce methadone dose. Discussion: The proposed mechanism of opioid-induced AI is the inhibitory effect on the hypothalamic-pituitary-adrenal axis, similar to the effect on the gonadal axis which causes hypogonadism. The risk for hypoglycemia is increased in patients taking more than 40 mg of oral methadone per day, and although the mechanism remains unclear, it is independent of adrenal function. Our patient had adrenal insufficiency and hypoglycemia related to methadone, which was further complicated by malnutrition. The glycogenic hepatopathy is a benign reversible condition that is believed to be a consequence of fluctuation in glucose levels. Conclusion: Given the life-threatening nature of adrenal crisis and the overlap in symptomatology with opiate overdose, clinicians should be prompt in evaluating for endocrinopathies in patients on chronic high dose opiates, and patients should be appropriately counseled on the potential consequences of methadone use. References: 1.Flory, J. H., et al. (2016). Methadone use and the risk of hypoglycemia for inpatients with cancer pain. JPSM, 51(1), 79–87.2.Li, T. et al. (2020). Prevalence of Opioid-Induced Adrenal Insufficiency in Patients Taking Chronic Opioids. JCEM, 105(10), dgaa499.

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Tran, Phu N., Jiansong Sheng, Aaron L. Randolph, Claudia Alvarez Baron, Nicolas Thiebaud, Ming Ren, Min Wu, et al. "Mechanisms of QT prolongation by buprenorphine cannot be explained by direct hERG channel block." PLOS ONE 15, no. 11 (November 6, 2020): e0241362. http://dx.doi.org/10.1371/journal.pone.0241362.

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Buprenorphine is a μ-opioid receptor (MOR) partial agonist used to manage pain and addiction. QTC prolongation that crosses the 10 msec threshold of regulatory concern was observed at a supratherapeutic dose in two thorough QT studies for the transdermal buprenorphine product BUTRANS®. Because QTC prolongation can be associated with Torsades de Pointes (TdP), a rare but potentially fatal ventricular arrhythmia, these results have led to further investigation of the electrophysiological effects of buprenorphine. Drug-induced QTC prolongation and TdP are most commonly caused by acute inhibition of hERG current (IhERG) that contribute to the repolarizing phase of the ventricular action potentials (APs). Concomitant inhibition of inward late Na+ (INaL) and/or L-type Ca2+ (ICaL) current can offer some protection against proarrhythmia. Therefore, we characterized the effects of buprenorphine and its major metabolite norbuprenorphine on cardiac hERG, Ca2+, and Na+ ion channels, as well as cardiac APs. For comparison, methadone, a MOR agonist associated with QTC prolongation and high TdP risk, and naltrexone and naloxone, two opioid receptor antagonists, were also studied. Whole cell recordings were performed at 37°C on cells stably expressing hERG, CaV1.2, and NaV1.5 proteins. Microelectrode array (MEA) recordings were made on human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). The results showed that buprenorphine, norbuprenorphine, naltrexone, and naloxone had no effect on IhERG, ICaL, INaL, and peak Na+ current (INaP) at clinically relevant concentrations. In contrast, methadone inhibited IhERG, ICaL, and INaL. Experiments on iPSC-CMs showed a lack of effect for buprenorphine, norbuprenorphine, naltrexone, and naloxone, and delayed repolarization for methadone at clinically relevant concentrations. The mechanism of QTC prolongation is opioid moiety-specific. This remains undefined for buprenorphine, while for methadone it involves direct hERG channel block. There is no evidence that buprenorphine use is associated with TdP. Whether this lack of TdP risk can be generalized to other drugs with QTC prolongation not mediated by acute hERG channel block warrants further study.

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Brawanski, Konstantin, Gero Brockhoff, Peter Hau, Arabel Vollmann-Zwerenz, Christian Freyschlag, Annette Lohmeier, Markus J. Riemenschneider, Claudius Thomé, Alexander Brawanski, and Martin A. Proescholdt. "Efficacy of D,L-methadone in the treatment of glioblastoma in vitro." CNS Oncology 7, no. 3 (July 2018): CNS18. http://dx.doi.org/10.2217/cns-2018-0006.

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33

Glanz, Morton, Sidney Klawansky, William McAullife, and Thomas Chalmers. "Methadone vs. L-alpha-acetylmethadol (LAAM) in the Treatment of Opiate Addiction." American Journal on Addictions 6, no. 4 (October 1997): 339–49. http://dx.doi.org/10.1111/j.1521-0391.1997.tb00415.x.

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34

Goldberg, Joel S. "Stereochemical Basis for a Unified Structure Activity Theory of Aromatic and Heterocyclic Rings in Selected Opioids and Opioid Peptides." Perspectives in Medicinal Chemistry 4 (January 2010): PMC.S3898. http://dx.doi.org/10.4137/pmc.s3898.

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This paper presents a novel unified theory of the structure activity relationship of opioids and opioid peptides. It is hypothesized that a virtual or known heterocyclic ring exists in all opioids which have activity in humans, and this ring occupies relative to the aromatic ring of the drug, approximately the same plane in space as the piperidine ring of morphine. Since the rings of morphine are rigid, and the aromatic and piperidine rings are critical structural components for morphine's analgesic properties, the rigid morphine molecule allows for approximations of the aromatic and heterocyclic relationships in subsequent drug models where bond rotations are common. This hypothesis and five propositions are supported by stereochemistry and experimental observations. Proposition #1 The structure of morphine provides a template. Proposition #2 Steric hindrance of some centric portion of the piperidine ring explains antagonist properties of naloxone, naltrexone and alvimopam. Proposition #3 Methadone has an active conformation which contains a virtual heterocyclic ring which explains its analgesic activity and racemic properties. Proposition #4 The piperidine ring of fentanyl can assume the morphine position under conditions of nitrogen inversion. Proposition #5 The first 3 amino acid sequences of beta endorphin (l-try-gly-gly) and the active opioid dipeptide, l-tyr-pro, (as a result of a peptide turn and zwitterion bonding) form a virtual piperazine-like ring which is similar in size, shape and location to the heterocyclic rings of morphine, meperidine, and methadone. Potential flaws in this theory are discussed. This theory could be important for future analgesic drug design.

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35

Hiltunen, A. J., O. Beck, P. Hjemdahl, P. Liljeberg, U. Almstr�m, K. Brodin, J. von Wachenfeldt, and S. Borg. "Rated well-being in relation to plasma concentrations of l - and d -methadone in satisfied and dissatisfied patients on methadone maintenance treatment." Psychopharmacology 143, no. 4 (April 26, 1999): 385–93. http://dx.doi.org/10.1007/s002130050963.

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36

Wilson, J. F., B. L. Smith, P. A. Toseland, J. Williams, D. Burnett, A. D. Hirst, I. D. Watson, and A. N. Horn. "External Quality Assessment of Techniques for the Detection of Drugs of Abuse in Urine." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 31, no. 4 (July 1994): 335–42. http://dx.doi.org/10.1177/000456329403100405.

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Five chromatographic and six immunoassay techniques were compared using data reported by 131 participants in the UK National External Quality Assessment Scheme for Drugs of Abuse in Urine. Twenty Five samples were studied containing none or one of three concentrations of amphetamine, barbiturates, benzodiazepines, benzoylecgonine, methadone and morphine. Technique sensitivity and specificity achieved with realistic clinical samples of 25 mL vol were assessed as the percentage of true positive and true negative tests, respectively. Thin-layer chromatography was inadequate for the detection of several analytes, the sensitivity for 0 · 5 mg/L of benzoylecgonine being < 30%, and for 1 · 5 mg/L of amphetamine < 86%. Gas chromatography with mass spectrometry was significantly less sensitive than other techniques for the detection of 0·5 mg/L of benzoylecgonine (71%) and 1 · 5 mg/L of morphine (88%). High-performance liquid chromatography was the most sensitive for amphetamine. Immunoassays performed well when operating above then-specified cut-off concentrations but, because they are directed to quinalbarbitone showed reduced cross-reactivity with amylobarbitone, the barbiturate more commonly prescribed in the UK.

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Moukaddam, Nidal, David V. Herin, Angela Stotts, Anne Hamilton Dougherty, Charles Green, Marc Mooney, Ann Garcia, et al. "Comparison of 3 L-α-acetyl-methadol (LAAM) Maintenance Strategies for Heroin Dependence." Addictive Disorders & Their Treatment 8, no. 4 (December 2009): 191–200. http://dx.doi.org/10.1097/adt.0b013e3181848b04.

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38

Oppermann, Henry, Martina Matusova, Annegret Glasow, Johannes Dietterle, Rainer Baran-Schmidt, Karsten Neumann, Jürgen Meixensberger, and Frank Gaunitz. "d,l-Methadone does not improve radio- and chemotherapy in glioblastoma in vitro." Cancer Chemotherapy and Pharmacology 83, no. 6 (March 19, 2019): 1017–24. http://dx.doi.org/10.1007/s00280-019-03816-3.

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39

Cha, Y., and C. G. Pitt. "A one-week subdermal delivery system for l-methadone based on biodegradable microcapsules." Journal of Controlled Release 7, no. 1 (April 1988): 69–78. http://dx.doi.org/10.1016/0168-3659(88)90082-x.

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40

Sreenivasan, Gayatri M., Raymund L. M. Yong, and Dan Holmes. "Chronic Aluminum Toxicity Due to Intravenous Substance Abuse Managed with Deferoxamine Chelation Therapy: Case Report." Blood 104, no. 11 (November 16, 2004): 3695. http://dx.doi.org/10.1182/blood.v104.11.3695.3695.

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Abstract Aluminum toxicity first came to attention in the medical literature as a sequela of peritoneal or hemodialysis, where accumulation of aluminum in body tissues results from the use of aluminum-containing dialysate and phosphate binders. The most common clinical presentations of aluminum toxicity include anemia, bone disease, and a syndrome of encephalopathy known as the dialysis encephalopathy sydrome (DES). We present the unique case of a 42-year-old man who developed chronic aluminum toxicity from the intravenous injection of a methadone preparation intended for oral consumption. The methadone solution was concentrated for intravenous injection by heating in aluminum cookware. Experiments performed in our laboratory reproducing this technique, using weakly acidic solutions similar to popular drink mixes, confirmed that significant amounts of elemental aluminum can be leached from aluminum cookware when heated. The patient presented to medical attention with generalized seizures, profound cerebellar dysfunction, myoclonus, and speech apraxia, all of which are characteristic of DES. The peripheral blood film revealed bizarre red cell morphology, with clear features of iron deficiency and prominent coarse basophilic stippling, suggesting impaired iron utilization, which is at least one mechanism of aluminum related hematologic toxicity. A bone marrow biopsy demonstrated extensive osteosclerosis and myelosclerosis, compatible with significant metabolic bone disease. Subsequent investigations revealed a serum aluminum level of 7200 nmol/L, eighteen times the upper limit of normal (400 nmol/L). Chelation therapy with a continuous intravenous infusion of deferoxamine was started, and over a course of ten months the serum aluminum level was reduced to 2390 nmol/L with few side effects. The patient made a significant neurologic recovery and returned to life in the community. This is the first detailed account of the successful use of deferoxamine to chelate aluminum in a patient without dialysis-dependent renal insufficiency. This case also highlights heavy metal exposure as a diagnostic consideration in intravenous substance abusers presenting with multiorgan dysfunction, and the importance of performing a thorough inquiry into injection drug practices when evaluating these patients.

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Wedekind, Dirk, Stefan Jacobs, Iris Karg, Christel Luedecke, Udo Schneider, Konrad Cimander, Pierre Baumann, Eckart Ruether, Wolfgang Poser, and Ursula Havemann-Reinecke. "Psychiatric comorbidity and additional abuse of drugs in maintenance treatment withl- andd,l-methadone." World Journal of Biological Psychiatry 11, no. 2-2 (March 2010): 390–99. http://dx.doi.org/10.3109/15622970802176487.

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42

Raekallio, Marja R., Maija P. Räihä, Maarit H. Alanen, Nina M. Sarén, and Tove A. Tuovio. "Effects of medetomidine, l –methadone, and their combination on arterial blood gases in dogs." Veterinary Anaesthesia and Analgesia 36, no. 2 (March 2009): 158–61. http://dx.doi.org/10.1111/j.1467-2995.2008.00444.x.

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43

Stadlbauer, B., D. Kozian, C. Stief, and A. Buchner. "Co-treatment with L-methadone increases the efficacy of cytostatic drugs in prostate cancer cells." European Urology Supplements 16, no. 3 (March 2017): e1305. http://dx.doi.org/10.1016/s1569-9056(17)30809-6.

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44

Di Bella, Caterina, Luca Lacitignola, Laura Fracassi, Despoina Skouropoulou, Antonio Crovace, and Francesco Staffieri. "Pulse Pressure Variation Can Predict the Hemodynamic Response to Pneumoperitoneum in Dogs: A Retrospective Study." Veterinary Sciences 6, no. 1 (February 20, 2019): 17. http://dx.doi.org/10.3390/vetsci6010017.

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Pneumoperitoneum may induce important hemodynamic alterations in healthy subjects. Pulse pressure variation (PPV) is a hemodynamic parameter able to discriminate preload dependent subjects. Anesthesia records of dogs undergoing laparoscopy were retrospectively evaluated. The anesthetic protocol included acepromazine, methadone, propofol and isoflurane administered with oxygen under mechanical ventilation. The hemodynamic parameters were considered five minutes before (BASE) and ten minutes after (P10) the pneumoperitoneum. Based on the cardiac index (CI) variation, at P10, dogs were classified as sensitive (S group, CI ≤ 15%) and non-sensitive (NO-S group). Data were analyzed with the ANOVA test and the ROC curve (p < 0.05). Fifty-five percent of dogs (S) had a reduction of CI ≥ 15% at P10 (2.97 ± 1.4 L/min/m2) compared to BASE (4.32 ± 1.62 L/min/m2) and at P10 in the NO-S group (4.51 ± 1.41 L/min/m2). PPV at BASE was significantly higher in the S group (22.4% ± 6.1%) compared to the NO-S group (10.9% ± 3.3%). The ROC curve showed a threshold of PPV > 16% to distinguish the S and NO-S groups. PPV may be a valid predictor of the hemodynamic response to pneumoperitoneum in dogs. A PPV > 16% can identify patients that may require fluid administration before the creation of pneumoperitoneum.

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45

Øiestad, Elisabeth Leere, Unni Johansen, and Asbjorg Solberg Christophersen. "Drug Screening of Preserved Oral Fluid by Liquid Chromatography–Tandem Mass Spectrometry." Clinical Chemistry 53, no. 2 (February 1, 2007): 300–309. http://dx.doi.org/10.1373/clinchem.2006.074237.

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Abstract Background: Oral fluid is an alternative matrix with potential applications in road-side drug screening, work-place testing, drug treatment programs, and epidemiological surveys. Development of methods for extensive drug screening in oral fluid is warranted. Methods: We developed a liquid chromatography– tandem mass spectrometry (LC-MS/MS) method for drug screening of preserved oral fluid collected with the Intercept® collection device. Samples were prepared by liquid–liquid extraction with ethylacetate/heptane (4:1). LC-separation was achieved with an Atlantis dC18-column (2.1 × 50 mm, 3 μm particle). Mass detection was performed by positive ion mode electrospray LC-MS/MS and included the following drugs/metabolites: morphine, 6-monoacetylmorphine, codeine, buprenorphine, methadone, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, cocaine, benzoylecgonine, Δ-9-tetrahydrocannabinol, lysergic acid diethylamide, alprazolam, bromazepam, clonazepam, 7-aminoclonazepam, diazepam, N-desmethyldiazepam, 3-OH-diazepam, fenazepam, flunitrazepam, 7-aminoflunitrazepam, lorazepam, nitrazepam, 7-aminonitrazepam, oxazepam, zopiclone, zolpidem, carisoprodol, and meprobamat. Results: Screening of 32 drugs was performed with a run time of 14 min. Within- and between-day relative CVs varied from 2.0% to 31.8% and from 3.6% to 39.1%, respectively. Extraction recoveries were >50% except for morphine (30%) and benzoylecgonine (0.2%). The concentrations of the lowest calibrator were 1 nmol/L (0.28 μg/L) to 500 nmol/L (68 μg/L), depending on the drug. Conclusion: The method allowed rapid and sensitive oral fluid screening for the most commonly abused drugs in Norway and will be used for a road-side survey of drug use in normal traffic.

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Deeb, Shaza, Fiona M. Wylie, Hazel J. Torrance, and Karen S. Scott. "An Insight into Gabapentin and Pregabalin in Scottish Prisoners." Journal of Analytical Toxicology 44, no. 5 (February 1, 2020): 504–13. http://dx.doi.org/10.1093/jat/bkz105.

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Abstract The aim of this study was to evaluate the prevalence and abuse potential of antiepileptic drugs (AEDs) among prison populations in Scotland, UK. Participants consisted of all admitted and released prisoners over a 1 month period who consented to provide samples. Urine samples were collected and analyzed by liquid chromatography coupled with triple quadrupole tandem mass spectrometry using a method validated for the simultaneous quantification of 21 AEDs in urine. A total of 904 samples were collected. The samples were also screened for drugs of abuse by using point-of-care testing kits. A total of 18% of the samples were positive for AEDs. Gabapentin (GBP) was identified in 118 samples (13%) and pregabalin (PRG) in 32 samples (3.5%). Interestingly, 12 samples contained both drugs (1.3%). The concentrations ranged from 0.5 to 1,100 mg/L (median, 15 mg/L) for GBP and from 0.5 to 440 mg/L (median, 7.3 mg/L) for PRG. Four samples were found to have concentrations >400 mg/L, two samples for GBP and two samples for PRG. These concentrations are at least 20 times above the median concentrations. Other AEDs detected were levetiracetam (four samples), vigabatrin (four samples), lamotrigine (three samples), valproic acid (three samples), carbamazepine (two samples) and topiramate (one sample). Illicit or non-prescribed drugs were detected in 81% of urine samples of which 80% were from admitted prisoners and 20% from released prisoners. Benzodiazepines, opiates and cannabis were the most frequently detected drugs. Other drugs found in positive AED samples were methadone (26%), cocaine (18%), buprenorphine (17%), amphetamines (4%), methamphetamines (4%) and barbiturates (4%). This study shows a high prevalence of AEDs within the Scottish prison system, primarily due to GBP and PRG; however, due to the anonymity of the sample collection, it is unknown if these are prescribed or illicit drug ingestions.

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FISCHER, B., K. CARRIGAN, and L. DYKSTRA. "Effects of -Methyl-D-Aspartate Receptor Antagonists on Acute Morphine-Induced and l-Methadone-Induced Antinociception in Mice." Journal of Pain 6, no. 7 (July 2005): 425–33. http://dx.doi.org/10.1016/j.jpain.2005.02.003.

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48

Sabatowski, Rainer, Stefan M. Kasper, and Lukas Radbruch. "Patient-Controlled Analgesia With Intravenous L-Methadone in a Child With Cancer Pain Refractory to High-Dose Morphine." Journal of Pain and Symptom Management 23, no. 1 (January 2002): 3–5. http://dx.doi.org/10.1016/s0885-3924(01)00389-x.

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Glanz, Morton, Sidney Klawansky, William McAullife, and Thomas Chalmers. "Methadone vs. L-alpha-acetylmethadol (LAAM) in the Treatment of Opiate Addiction:A Meta-Analysis of the Randomized, Controlled TriaIs." American Journal on Addictions 6, no. 4 (January 1997): 339–49. http://dx.doi.org/10.3109/10550499709005065.

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50

Margolin, Arthur, Michael Copenhaver, S. Kelly Avants, and Kathleen Kantak. "A Preliminary, Controlled Investigation of Magnesium L-Aspartate Hydrochloride for Illicit Cocaine and Opiate Use in Methadone-Maintained Patients." Journal of Addictive Diseases 22, no. 2 (April 2003): 49–61. http://dx.doi.org/10.1300/j069v22n02_04.

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