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1

Claret, Laurent, and Athanassios Iliadis. "Nonparametric density estimation applied to population pharmacokinetics." Mathematical Biosciences 133, no. 1 (1996): 51–68. http://dx.doi.org/10.1016/0025-5564(95)00079-8.

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2

Vincze, István, Rita Czermann, Zsuzsanna Nagy, et al. "Assessment of Antibiotic Pharmacokinetics, Molecular Biomarkers and Clinical Status in Critically Ill Adults Diagnosed with Community-Acquired Pneumonia and Receiving Intravenous Piperacillin/Tazobactam and Hydrocortisone over the First Five Days of Intensive Care: An Observational Study (STROBE Compliant)." Journal of Clinical Medicine 11, no. 14 (2022): 4140. http://dx.doi.org/10.3390/jcm11144140.

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Severe community-acquired pneumonia (CAP) is a condition that frequently requires intensive care and, eventually, can cause to death. Piperacillin/tazobactam antibiotic therapy is employed as an empiric intravenous regimen, in many cases supplemented with intravenous bolus hydrocortisone treatment. The individual and condition-dependent pharmacokinetic properties of these drugs may lead to therapeutic failure. The impact of systemic inflammation, as well as of hydrocortisone on the altered pharmacokinetics of piperacillin is largely unknown. The protocol of a clinical study aimed at the charac
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3

Hope, William W. "Population Pharmacokinetics of Voriconazole in Adults." Antimicrobial Agents and Chemotherapy 56, no. 1 (2011): 526–31. http://dx.doi.org/10.1128/aac.00702-11.

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ABSTRACTVoriconazole is a first-line agent for the treatment of invasive fungal infections. The pharmacology of voriconazole is characterized by extensive interindividual variability and nonlinear pharmacokinetics. The population pharmacokinetics of voriconazole in 64 adults is described. The patient population consisted of 21 healthy volunteers, who received a range of intravenous (i.v.) and oral voriconazole regimens, and 43 patients with proven or probable invasive aspergillosis, who received the currently licensed dosage. Voriconazole concentrations were measured using high-performance liq
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4

Jelliffe, Roger, Alan Schumitzky, and Michael Van Guilder. "Population Pharmacokinetics/Pharmacodynamics Modeling: Parametric and Nonparametric Methods." Therapeutic Drug Monitoring 22, no. 3 (2000): 354–65. http://dx.doi.org/10.1097/00007691-200006000-00019.

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5

Bourguignon, Laurent, Yoann Cazaubon, Guillaume Debeurme, Constance Loue, Michel Ducher, and Sylvain Goutelle. "Pharmacokinetics of Vancomycin in Elderly Patients Aged over 80 Years." Antimicrobial Agents and Chemotherapy 60, no. 8 (2016): 4563–67. http://dx.doi.org/10.1128/aac.00303-16.

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ABSTRACTSince the 1950s, vancomycin has remained a reference treatment for severe infections caused by Gram-positive bacteria, including methicillin-resistantStaphylococcus aureus. Vancomycin is a nephrotoxic and ototoxic drug mainly eliminated through the kidneys. It has a large interindividual pharmacokinetic variability, which justifies monitoring its plasma concentrations in patients. This is especially important in patients aged over 80 years, who frequently have renal impairment. However, the pharmacokinetics of vancomycin in this population is very poorly described in the literature. Th
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Karvaly, Gellért Balázs, István Vincze, Michael Noel Neely, et al. "Modeling Pharmacokinetics in Individual Patients Using Therapeutic Drug Monitoring and Artificial Population Quasi-Models: A Study with Piperacillin." Pharmaceutics 16, no. 3 (2024): 358. http://dx.doi.org/10.3390/pharmaceutics16030358.

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Population pharmacokinetic (pop-PK) models constructed for model-informed precision dosing often have limited utility due to the low number of patients recruited. To augment such models, an approach is presented for generating fully artificial quasi-models which can be employed to make individual estimates of pharmacokinetic parameters. Based on 72 concentrations obtained in 12 patients, one- and two-compartment pop-PK models with or without creatinine clearance as a covariate were generated for piperacillin using the nonparametric adaptive grid algorithm. Thirty quasi-models were subsequently
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7

Vanhove, G. F., H. Kastrissios, J. M. Gries, et al. "Pharmacokinetics of saquinavir, zidovudine, and zalcitabine in combination therapy." Antimicrobial Agents and Chemotherapy 41, no. 11 (1997): 2428–32. http://dx.doi.org/10.1128/aac.41.11.2428.

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We investigated the pharmacokinetics of zidovudine, zalcitabine, and saquinavir in AIDS Clinical Trial Group protocol 229. Patients received either saquinavir, zalcitabine, or a combination of both, together with zidovudine three times a day. Approximately 100 patients were enrolled in each treatment arm, and intensive pharmacokinetic studies were performed on about 25 patients per arm at weeks 1 and 12. We estimated the pharmacokinetic parameters of all three drugs by using parametric and nonparametric methods. The mean values of the pharmacokinetic parameters of zidovudine (clearance [CL]/bi
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8

Egan, Talmage D., Amarnath Sharma, Michael A. Ashburn, Jur Kievit, Nathan L. Pace, and James B. Streisand. "Multiple Dose Pharmacokinetics of Oral Transmucosal Fentanyl Citrate in Healthy Volunteers." Anesthesiology 92, no. 3 (2000): 665–73. http://dx.doi.org/10.1097/00000542-200003000-00009.

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Background Oral transmucosal fentanyl citrate (OTFC) is a solid form of fentanyl that delivers the drug through the oral mucosa. The clinical utility of multiple doses of OTFC in the treatment of "breakthrough" cancer pain is under evaluation. The aim of this study was to test the hypothesis that the pharmacokinetics of OTFC do not change with multiple dosing. Methods Twelve healthy adult volunteers received intravenous fentanyl (15 microg/kg) or OTFC (three consecutive doses of 800 microg) on separate study sessions. Arterial blood samples were collected for determination of fentanyl plasma c
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9

Yamada, Walter M., Michael N. Neely, Jay Bartroff, et al. "An Algorithm for Nonparametric Estimation of a Multivariate Mixing Distribution with Applications to Population Pharmacokinetics." Pharmaceutics 13, no. 1 (2020): 42. http://dx.doi.org/10.3390/pharmaceutics13010042.

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Population pharmacokinetic (PK) modeling has become a cornerstone of drug development and optimal patient dosing. This approach offers great benefits for datasets with sparse sampling, such as in pediatric patients, and can describe between-patient variability. While most current algorithms assume normal or log-normal distributions for PK parameters, we present a mathematically consistent nonparametric maximum likelihood (NPML) method for estimating multivariate mixing distributions without any assumption about the shape of the distribution. This approach can handle distributions with any shap
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10

Neely, Michael, Ashley Margol, Xiaowei Fu, et al. "Achieving Target Voriconazole Concentrations More Accurately in Children and Adolescents." Antimicrobial Agents and Chemotherapy 59, no. 6 (2015): 3090–97. http://dx.doi.org/10.1128/aac.00032-15.

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ABSTRACTDespite the documented benefit of voriconazole therapeutic drug monitoring, nonlinear pharmacokinetics make the timing of steady-state trough sampling and appropriate dose adjustments unpredictable by conventional methods. We developed a nonparametric population model with data from 141 previously richly sampled children and adults. We then used it in our multiple-model Bayesian adaptive control algorithm to predict measured concentrations and doses in a separate cohort of 33 pediatric patients aged 8 months to 17 years who were receiving voriconazole and enrolled in a pharmacokinetic
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11

Garey, Kevin W., Charles A. Peloquin, Paul G. Godo, Anne N. Nafziger, and Guy W. Amsden. "Lack of Effect of Zafirlukast on the Pharmacokinetics of Azithromycin, Clarithromycin, and 14-Hydroxyclarithromycin in Healthy Volunteers." Antimicrobial Agents and Chemotherapy 43, no. 5 (1999): 1152–55. http://dx.doi.org/10.1128/aac.43.5.1152.

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ABSTRACT This randomized, open-label, crossover study was conducted to investigate whether the coadministration of zafirlukast would affect the pharmacokinetics of azithromycin, clarithromycin, or 14-hydroxyclarithromycin (14-OHC). Twelve healthy subjects (six males and six females) received single 500-mg doses of azithromycin and clarithromycin with and without zafirlukast given to a steady-state concentration. Blood was collected prior to all macrolide doses and for 3 and 10 days after each clarithromycin and azithromycin dose, respectively. Serum was assayed for azithromycin, clarithromycin
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12

Charles, Bruce G., Ann K. Miller, Peter E. Nasveld, Mark G. Reid, Ivor E. Harris, and Michael D. Edstein. "Population Pharmacokinetics of Tafenoquine during Malaria Prophylaxis in Healthy Subjects." Antimicrobial Agents and Chemotherapy 51, no. 8 (2007): 2709–15. http://dx.doi.org/10.1128/aac.01183-06.

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ABSTRACT The population pharmacokinetics of tafenoquine were studied in Australian soldiers taking tafenoquine for malarial prophylaxis. The subjects (476 males and 14 females) received a loading dose of 200 mg tafenoquine base daily for 3 days, followed by a weekly dose of 200 mg tafenoquine for 6 months. Blood samples were collected from each subject after the last loading dose and then at weeks 4, 8, and 16. Plasma tafenoquine concentrations were determined by liquid chromatography-tandem mass spectrometry. Population modeling was performed with NONMEM, using a one-compartment model. Typica
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13

Jerling, Markus, Yann Merlé, France Mentré, and Alain Mallet. "Population pharmacokinetics of clozapine evaluated with the nonparametric maximum likelihood method." British Journal of Clinical Pharmacology 44, no. 5 (1997): 447–53. http://dx.doi.org/10.1046/j.1365-2125.1997.t01-1-00606.x.

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14

Inciardi, J. F., and K. K. Batra. "Nonparametric approach to population pharmacokinetics in oncology patients receiving aminoglycoside therapy." Antimicrobial Agents and Chemotherapy 37, no. 5 (1993): 1025–27. http://dx.doi.org/10.1128/aac.37.5.1025.

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15

Mallet, Alain, France Mentré, Jean Louis Steimer, and François Lokiec. "Nonparametric maximum likelihood estimation for population pharmacokinetics, with application to cyclosporine." Journal of Pharmacokinetics and Biopharmaceutics 16, no. 3 (1988): 311–27. http://dx.doi.org/10.1007/bf01062140.

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16

Tréluyer, J. M., Y. Merlé, S. Tonnelier, E. Rey, and G. Pons. "Nonparametric Population Pharmacokinetic Analysis of Amikacin in Neonates, Infants, and Children." Antimicrobial Agents and Chemotherapy 46, no. 5 (2002): 1381–87. http://dx.doi.org/10.1128/aac.46.5.1381-1387.2002.

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ABSTRACT The therapeutic and toxic effects of amikacin are known to depend on its concentration in plasma, but the pharmacokinetics of this drug in neonates, infants, and children and the influences of clinical and biological variables have been only partially assessed. Therapeutic drug monitoring data collected from 155 patients (49 neonates, 77 infants, and 29 children) receiving amikacin were analyzed by a nonparametric population-based approach, the nonparametric maximum-likelihood method. We assessed the effects of gestational and postnatal age, weight, Apgar score, and plasma creatinine
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17

Matar, Kamal M., Yousef Al-lanqawi, Kefaya Abdul-Malek, and Roger Jelliffe. "Amikacin Population Pharmacokinetics in Critically Ill Kuwaiti Patients." BioMed Research International 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/202818.

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Amikacin pharmacokinetic data in Kuwaiti (Arab) intensive care unit (ICU) patients are lacking. Fairly sparse serum amikacin peak and trough concentrations data were obtained from adult Kuwaiti ICU patients. The data were analysed using a nonparametric adaptive grid (NPAG) maximum likelihood algorithm. The estimations of the developed model were assessed using mean error (ME) as a measure of bias and mean squared error (MSE) as a measure of precision. A total of 331 serum amikacin concentrations were obtained from 56 patients. The mean (±SD) model parameter values found wereVc= 0.2302 ± 0.0866
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18

Vinks, Alexander A., Jan G. den Hollander, Shelley E. Overbeek, Roger W. Jelliffe, and Johan W. Mouton. "Population Pharmacokinetic Analysis of Nonlinear Behavior of Piperacillin during Intermittent or Continuous Infusion in Patients with Cystic Fibrosis." Antimicrobial Agents and Chemotherapy 47, no. 2 (2003): 541–47. http://dx.doi.org/10.1128/aac.47.2.541-547.2003.

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ABSTRACT The purpose of this study was to describe the nonlinear pharmacokinetics of piperacillin observed during intermittent infusion and continuous infusion by using a nonparametric population modeling approach. Data were 120 serum piperacillin concentration measurements from eight adult cystic fibrosis (CF) patients. Individual pharmacokinetic parameter estimates during intermittent infusion or continuous infusion were calculated by noncompartmental analysis and with a maximum iterative two-stage Bayesian estimator. To simultaneously describe concentration-time data during intermittent inf
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19

Karvaly, Gellért Balázs, István Vincze, Alexandra Balogh, Zoltán Köllő, Csaba Bödör, and Barna Vásárhelyi. "A High-Throughput Clinical Laboratory Methodology for the Therapeutic Monitoring of Ibrutinib and Dihydrodiol Ibrutinib." Molecules 27, no. 15 (2022): 4766. http://dx.doi.org/10.3390/molecules27154766.

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Ibrutinib (IBR) is an oral anticancer medication that inhibits Bruton tyrosine kinase irreversibly. Due to the high risk of adverse effects and its pharmacokinetic variability, the safe and effective use of IBR is expected to be facilitated by precision dosing. Delivering suitable clinical laboratory information on IBR is a prerequisite of constructing fit-for-purpose population and individual pharmacokinetic models. The validation of a dedicated high-throughput method using liquid chromatography–mass spectrometry is presented for the simultaneous analysis of IBR and its pharmacologically acti
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20

Wang, Yang, Dan Sun, Yan Mei, et al. "Population Pharmacokinetics and Dosing Regimen Optimization of Latamoxef in Chinese Children." Pharmaceutics 14, no. 5 (2022): 1033. http://dx.doi.org/10.3390/pharmaceutics14051033.

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The present study aimed to establish population pharmacokinetic models of latamoxef, as well as its R- and S-epimers, and generate findings to guide the individualized administration of latamoxef in pediatric patients. A total of 145 in-hospital children aged 0.08–10.58 years old were included in this study. Three population pharmacokinetic models of latamoxef and its R- and S-epimers were established. The stability and predictive ability of the final models were evaluated by utilizing goodness-of-fit plots, nonparametric bootstrapping, and normalized prediction distribution errors. The final
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21

Unadkat, Jashvant D., Ferenc Bartha, and Lewis B. Sheiner. "Simultaneous modeling of pharmacokinetics and pharmacodynamics with nonparametric kinetic and dynamic models." Clinical Pharmacology and Therapeutics 40, no. 1 (1986): 86–93. http://dx.doi.org/10.1038/clpt.1986.143.

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22

Davidian, Marie, and A. Ronald Gallant. "Smooth nonparametric maximum likelihood estimation for population pharmacokinetics, with application to quinidine." Journal of Pharmacokinetics and Biopharmaceutics 20, no. 5 (1992): 529–56. http://dx.doi.org/10.1007/bf01061470.

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23

Vinks, A. A., J. W. Mouton, D. J. Touw, H. G. Heijerman, M. Danhof, and W. Bakker. "Population pharmacokinetics of ceftazidime in cystic fibrosis patients analyzed by using a nonparametric algorithm and optimal sampling strategy." Antimicrobial Agents and Chemotherapy 40, no. 5 (1996): 1091–97. http://dx.doi.org/10.1128/aac.40.5.1091.

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Postinfusion data obtained from 17 patients with cystic fibrosis participating in two clinical trials were used to develop population models for ceftazidime pharmacokinetics during continuous infusion. Determinant (D)-optimal sampling strategy (OSS) was used to evaluate the benefits of merging four maximally informative sampling times with population modeling. Full and sparse D-optimal sampling data sets were analyzed with the nonparametric expectation maximization (NPEM) algorithm and compared with the model obtained by the traditional standard two-stage approach. Individual pharmacokinetic p
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24

Hung, Daniel Y., Gerhard A. Siebert, Ping Chang, et al. "Hepatic pharmacokinetics of propranolol in rats with adjuvant-induced systemic inflammation." American Journal of Physiology-Gastrointestinal and Liver Physiology 290, no. 2 (2006): G343—G351. http://dx.doi.org/10.1152/ajpgi.00155.2005.

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Systemic inflammation is known to affect drug disposition in the liver. This study sought to relate and quantitate changes in hepatic pharmacokinetics of propranolol with changes in hepatic architecture and physiology in adjuvant-treated rats. Transmission electron microscopy was used to assess morphological changes in mitochondria and lysosomes of adjuvant-treated rat livers. The disposition of propranolol was assessed in the perfused rat liver using the multiple indicator dilution technique. Hepatic extraction and mean transit time were determined from outflow-concentration profiles using a
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25

Elhence, Hirsh, Kanokporn Mongkolrattanothai, Sindhu Mohandas, and Michael N. Neely. "Isavuconazole Pharmacokinetics and Pharmacodynamics in Children." Pharmaceutics 15, no. 1 (2022): 75. http://dx.doi.org/10.3390/pharmaceutics15010075.

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Isavuconazole is a broad-spectrum azole anti-fungal not yet approved in children. We conducted a retrospective, single-center review of isavuconazole use and routine therapeutic drug monitoring in pediatric patients, extracting demographic, dosing, concentration, mortality and hepatoxicity data. We constructed a nonparametric population model using Pmetrics. Of 26 patients, 19 (73%) were male. The mean (SD) age and weight were 12.7 (5.5) years and 50.9 (26.8) kg. Eighty percent received between 9.7 and 10.6 mg/kg per dose. Ten (38%) subjects had proven fungal disease and eight (31%) had probab
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26

Segal, Jack L., Thomas M. Oilman, and Sherry R. Brunnemann. "A NONPARAMETRIC ALTERNATIVE TO MODELING POPULATION PHARMACOKINETICS IN PATIENTS WITH SPINAL CORD INJURY." American Journal of Therapeutics 2, no. 2 (1995): 100–105. http://dx.doi.org/10.1097/00045391-199502000-00004.

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27

Vinks, Alexander A., Ronald N. van Rossem, Ron A. A. Mathôt, Harry G. M. Heijerman, and Johan W. Mouton. "Pharmacokinetics of Aztreonam in Healthy Subjects and Patients with Cystic Fibrosis and Evaluation of Dose-Exposure Relationships Using Monte Carlo Simulation." Antimicrobial Agents and Chemotherapy 51, no. 9 (2007): 3049–55. http://dx.doi.org/10.1128/aac.01522-06.

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ABSTRACT Aztreonam (AZM) is a monobactam antibiotic with a high level of activity against gram-negative micro-organisms, including Pseudomonas aeruginosa. We evaluated AZM pharmacokinetics and pharmacokinetic-pharmacodynamic relationships in patients with cystic fibrosis (CF) and healthy subjects. Pharmacokinetic data in eight CF patients and healthy subjects that were matched for age, gender, weight, and height were obtained and analyzed by using the nonparametric adaptive grid algorithm. Probabilities of target attainment using percentages of time of unbound concentration above the MIC (fT&g
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28

Aquerreta, Irene, Azucena Aldaz, Joaquín Giráldez, and Luis Sierrasesúmaga. "Pharmacodynamics of High-Dose Methotrexate in Pediatric Patients." Annals of Pharmacotherapy 36, no. 9 (2002): 1344–50. http://dx.doi.org/10.1345/aph.1a446.

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OBJECTIVE: To establish a relationship between the pharmacokinetics of high-dose methotrexate (MTX) and toxicity in children of a pediatric oncology department and to reassess MTX concentrations at which the patients would be at high risk for toxic effects. METHODS: This study included 37 patients (227 treatment courses) who received a median dose of 4.87 g/m2 of MTX in a 4-hour infusion. The population pharmacokinetic parameters of MTX were estimated by parametric (IT2B) and nonparametric methods (NPEM). Gastrointestinal, renal, and hematologic toxicity were evaluated. The relationship betwee
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29

Goutelle, Sylvain, Jean‐Baptiste Woillard, Thierry Buclin, et al. "Parametric and Nonparametric Methods in Population Pharmacokinetics: Experts’ Discussion on Use, Strengths, and Limitations." Journal of Clinical Pharmacology 62, no. 2 (2021): 158–70. http://dx.doi.org/10.1002/jcph.1993.

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30

Mustafa, Suzana, Mohd Ali, Azhar Mohamed, et al. "Determination of vancomycin pharmacokinetics in critically ill intensive care unit patients in Malaysia: A population pharmacokinetic analysis with a nonparametric approach." National Journal of Physiology, Pharmacy and Pharmacology 8, no. 9 (2018): 1. http://dx.doi.org/10.5455/njppp.2018.8.1030815102018.

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31

Smith, Patrick F., Alan Forrest, Charles H. Ballow, David E. Martin, and Louise Proulx. "Safety, Tolerability, and Pharmacokinetics of Single Oral Doses of BCH-10652 in Healthy Adult Males." Antimicrobial Agents and Chemotherapy 44, no. 10 (2000): 2816–23. http://dx.doi.org/10.1128/aac.44.10.2816-2823.2000.

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ABSTRACT Racemic dOTC (BCH-10652) is a novel nucleoside reverse transcriptase inhibitor consisting of two enantiomers of 2′-deoxy-3′-oxa-4′-thiocytidine, (−)dOTC and (+)dOTC, that have both shown activity against human immunodeficiency virus type 1. The objectives of this study were to characterize the safety, tolerability, and stereospecific pharmacokinetics of single oral doses of racemic dOTC in healthy, nonsmoking adult male volunteers. Subjects received single oral doses of 100, 200, 400, 800, and 1,600 mg of racemic dOTC in a placebo-controlled, dose-rising, incomplete crossover study de
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32

Prémaud, A., L. T. Weber, B. Tönshoff, et al. "Population pharmacokinetics of mycophenolic acid in pediatric renal transplant patients using parametric and nonparametric approaches." Pharmacological Research 63, no. 3 (2011): 216–24. http://dx.doi.org/10.1016/j.phrs.2010.10.017.

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33

Corvaisier, Stéphane, Bruno Charpiat, Cyril Mounier, et al. "Population Pharmacokinetics of Pyrimethamine and Sulfadoxine in Children Treated for Congenital Toxoplasmosis." Antimicrobial Agents and Chemotherapy 48, no. 10 (2004): 3794–800. http://dx.doi.org/10.1128/aac.48.10.3794-3800.2004.

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ABSTRACT The population pharmacokinetics of pyrimethamine (PYR) and sulfadoxine (SDX) for a group of 32 children with congenital toxoplasmosis was investigated by nonparametric modeling analysis. A one-compartment model was used as the structural model, and individual pharmacokinetic parameters were estimated by Bayesian modeling. PYR (1.25 mg/kg of body weight) and SDX (25 mg/kg) were administered orally every 10 days for 1 year, with adjustment of the dose to body weight every 3 months. Drug concentrations were measured by high-performance liquid chromatography. A total of 101 measurements i
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Goutelle, Sylvain, Laurent Bourguignon, Pascal H. Maire, Michael Van Guilder, John E. Conte, and Roger W. Jelliffe. "Population Modeling and Monte Carlo Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Rifampin in Lungs." Antimicrobial Agents and Chemotherapy 53, no. 7 (2009): 2974–81. http://dx.doi.org/10.1128/aac.01520-08.

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ABSTRACT Little information exists on the pulmonary pharmacology of antituberculosis drugs. We used population pharmacokinetic modeling and Monte Carlo simulation to describe and explore the pulmonary pharmacokinetics and pharmacodynamics of rifampin (RIF; rifampicin). A population pharmacokinetic model that adequately described the plasma, epithelial lining fluid (ELF), and alveolar cell (AC) concentrations of RIF in a population of 34 human volunteers was made by use of the nonparametric adaptive grid (NPAG) algorithm. The estimated concentrations correlated well with the measured concentrat
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Tam, Vincent H., Peggy S. McKinnon, Ronda L. Akins, George L. Drusano, and Michael J. Rybak. "Pharmacokinetics and Pharmacodynamics of Cefepime in Patients with Various Degrees of Renal Function." Antimicrobial Agents and Chemotherapy 47, no. 6 (2003): 1853–61. http://dx.doi.org/10.1128/aac.47.6.1853-1861.2003.

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ABSTRACT This study evaluated the pharmacokinetics of cefepime in 36 patients with different levels of renal function. Pharmacokinetic and pharmacodynamic parameters were calculated using samples obtained at steady state. Patients with creatinine clearance (CLCR) of >100 ml/min had more rapid clearance (CL) and a lower minimum concentration in serum (C min). C min in this group was found to be 3.3 ± 3.6 mg/liter (mean and standard deviation), compared to 19.5 ± 21.5 mg/liter in patients with a CLCR of between 60 and 100 ml/min (P = 0.025) and 14.0 ± 11.5 mg/liter in patients with a CLCR of
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Bondareva, I. B., R. W. Jelliffe, A. V. Sokolov, and I. F. Tischenkova. "Nonparametric population modeling of valproate pharmacokinetics in epileptic patients using routine serum monitoring data: implications for dosage." Journal of Clinical Pharmacy and Therapeutics 29, no. 2 (2004): 105–20. http://dx.doi.org/10.1111/j.1365-2710.2003.00538.x.

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37

Peloquin, C. A., G. S. Jaresko, C. L. Yong, A. C. Keung, A. E. Bulpitt, and R. W. Jelliffe. "Population pharmacokinetic modeling of isoniazid, rifampin, and pyrazinamide." Antimicrobial Agents and Chemotherapy 41, no. 12 (1997): 2670–79. http://dx.doi.org/10.1128/aac.41.12.2670.

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Isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) are the most important drugs for the treatment of tuberculosis (TB). The pharmacokinetics of all three drugs in the plasma of 24 healthy males were studied as part of a randomized cross-over phase I study of two dosage forms. Subjects ingested single doses of INH at 250 mg, RIF at 600 mg, and PZA at 1,500 mg. Plasma was collected for 36 h and was assayed by high-performance liquid chromatography. The data were analyzed by noncompartmental, iterative two-stage maximum a posteriori probability Bayesian (IT2B) and nonparametric expectation m
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38

Lo, Yoke-Lin, Johan G. C. van Hasselt, Siow-Chin Heng, Chin-Theam Lim, Toong-Chow Lee, and Bruce G. Charles. "Population Pharmacokinetics of Vancomycin in Premature Malaysian Neonates: Identification of Predictors for Dosing Determination." Antimicrobial Agents and Chemotherapy 54, no. 6 (2010): 2626–32. http://dx.doi.org/10.1128/aac.01370-09.

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ABSTRACT The present study determined the pharmacokinetic profile of vancomycin in premature Malaysian infants. A one-compartment infusion model with first-order elimination was fitted to serum vancomycin concentration data (n = 835 points) obtained retrospectively from the drug monitoring records of 116 premature newborn infants. Vancomycin concentrations were estimated by a fluorescence polarization immunoassay. Population and individual estimates of clearance and distribution volume and the factors which affected the variability observed for the values of these parameters were obtained usin
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J. Ibraheem Al-Tamimi, Jaafar. "Bioequivalence and Pharmacokinetics of Two Formulations of Amlodipine Tablets in Healthy Subjects." Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) 23, no. 1 (2017): 60–67. http://dx.doi.org/10.31351/vol23iss1pp60-67.

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The bioequivalence of a single dose tablet containing 5 mg amlodipine as a test product in comparison to Norvasc® 5 mg tablet (Pfizer USA) as the reference product was studied. Both products were administered to twenty eight healthy male adult subjects applying a fasting, single-dose, two-treatment, two-period, two-sequence, randomized crossover design with two weeks washout period between dosing. Twenty blood samples were withdrawn from each subject over 144 hours period. Amlodipine concentrations were determined in plasma by a validated HPLC-MS/MS method. From the plasma concentration-time
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Bulitta, J. B., C. B. Landersdorfer, M. Kinzig, U. Holzgrabe, and F. Sorgel. "New Semiphysiological Absorption Model To Assess the Pharmacodynamic Profile of Cefuroxime Axetil Using Nonparametric and Parametric Population Pharmacokinetics." Antimicrobial Agents and Chemotherapy 53, no. 8 (2009): 3462–71. http://dx.doi.org/10.1128/aac.00054-09.

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ABSTRACT Cefuroxime axetil is widely used to treat respiratory tract infections. We are not aware of a population pharmacokinetic (PK) model for cefuroxime axetil. Our objectives were to develop a semiphysiological population PK model and evaluate the pharmacodynamic profile for cefuroxime axetil. Twenty-four healthy volunteers received 250 mg oral cefuroxime as a suspension after a standardized breakfast. Liquid chromatography-tandem mass spectrometry was used for drug analysis, NONMEM and S-ADAPT (results reported) were used for parametric population PK modeling, and NPAG was used for nonpar
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Launay-Iliadis, M. C., R. Bruno, V. Cosson, et al. "Population pharmacokinetics of docetaxel during phase I studies using nonlinear mixed-effect modeling and nonparametric maximum-likelihood estimation." Cancer Chemotherapy and Pharmacology 37, no. 1-2 (1995): 47–54. http://dx.doi.org/10.1007/s002800050366.

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Launay-Iliadis, M. C., R. Bruno, V. Cosson, et al. "Population pharmacokinetics of docetaxel during phase I studies using nonlinear mixed-effect modeling and nonparametric maximum-likelihood estimation." Cancer Chemotherapy and Pharmacology 37, no. 1-2 (1995): 47–54. http://dx.doi.org/10.1007/bf00685628.

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Monogue, Marguerite L., Rebecca S. Pettit, Marianne Muhlebach, Jeffrey J. Cies, David P. Nicolau, and Joseph L. Kuti. "Population Pharmacokinetics and Safety of Ceftolozane-Tazobactam in Adult Cystic Fibrosis Patients Admitted with Acute Pulmonary Exacerbation." Antimicrobial Agents and Chemotherapy 60, no. 11 (2016): 6578–84. http://dx.doi.org/10.1128/aac.01566-16.

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ABSTRACTCeftolozane-tazobactam has potent activity againstPseudomonas aeruginosa, a pathogen associated with cystic fibrosis (CF) acute pulmonary exacerbations (APE). Due to the rapid elimination of many antibiotics, CF patients frequently have altered pharmacokinetics. In this multicenter, open-label study, we described the population pharmacokinetics and safety of ceftolozane-tazobactam at 3 g every 8 h (q8h) in 20 adult CF patients admitted with APE. Population pharmacokinetics were determined using the nonparametric adaptive grid program in Pmetrics for R. A 5,000-patient Monte Carlo simul
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Watling, Sharon M., and David F. Kisor. "Population Pharmacokinetics: Development of a Medical Intensive Care Unit-Specific Gentamicin Dosing Nomogram." Annals of Pharmacotherapy 27, no. 2 (1993): 151–54. http://dx.doi.org/10.1177/106002809302700202.

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Objective This study was designed to develop a population-specific dosing nomogram for gentamicin in medical intensive care unit (MICU) patients using the population pharmacokinetic program nonparametric expectation maximization (NPEM). Design Observational clinical gentamicin dosing data were collected, entered into the USC*PACK database program PASTRX, and downloaded into the population pharmacokinetic program NPEM. NPEM generated population pharmacokinetic parameter values that were used to develop a gentamicin dosing nomogram. The nomogram was tested in the next 15 patients admitted to MIC
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Alloul, Karine, David G. Whalley, Fanny Shutway, Zeyd Ebrahim, and France Varin. "Pharmacokinetic Origin of Carbamazepine-induced Resistance to Vecuronium Meeting Abstracts in Anesthetized Patients." Anesthesiology 84, no. 2 (1996): 330–39. http://dx.doi.org/10.1097/00000542-199602000-00010.

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Background Patients receiving chronic carbamazepine therapy have shortened recovery times from a neuromuscular block induced by vecuronium. The current study investigates the pharmacokinetic or pharmacodynamic mechanisms responsible for this observation. Methods Pharmacokinetics and pharmacodynamics of 0.1 mg/kg intravenous bolus vecuronium in ten epileptic patients receiving chronic carbamazepine therapy were compared to that of ten control subjects. All patients were scheduled for neurosurgery while anesthetized with isoflurane and sufentanil. Arterial blood samples were collected for 6 h. P
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Peloquin, Charles A., Amy E. Bulpitt, George S. Jaresko, Roger W. Jelliffe, Gordon T. James, and David E. Nix. "Pharmacokinetics of Pyrazinamide under Fasting Conditions, with Food, and with Antacids." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 18, no. 6 (1998): 1205–11. http://dx.doi.org/10.1002/j.1875-9114.1998.tb03138.x.

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Study Objectives. To determine intrasubject and intersubject variability in, and the effects of food and antacids on, the pharmacokinetics of pyrazinamide (PZA).Design. Randomized, four‐period, crossover phase I study.Subjects. Fourteen healthy men and women volunteers.Interventions. Subjects ingested single doses of PZA 30 mg/kg under fasting conditions twice, without a high‐fat meal and with an aluminum‐magnesium antacid. They also received standard dosages of isoniazid, rifampin, and ethambutol.Measurements and Main Results. Serum was collected for 48 hours and assayed by gas chromatography
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Hall, Ronald G., Jotam Pasipanodya, William C. Putnam, et al. "1319. Pharmacokinetics of Ceftolozane/Tazobactam in Patients with Burns." Open Forum Infectious Diseases 7, Supplement_1 (2020): S670—S671. http://dx.doi.org/10.1093/ofid/ofaa439.1501.

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Abstract Background Antimicrobial dosing in moderate/severe burns patients is complicated due to the potential unpredictable hyperdynamic pathophysiologic states including 1) hypoproteinemia, 2) acute kidney injury and 3) onset of septicemia. Therefore, distribution assumptions about the population pharmacokinetic (PopPK) profiles of either endogenous or xenobiotic pharmacophores in this patient population can lead to biased parameter estimates. In order to prevent potential bias an agnostic nonparametric adaptive grid approach to describe ceftolozane/tazobactam (C/T) PopPK profiles in patient
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Nicasio, Anthony M., Robert E. Ariano, Sheryl A. Zelenitsky, et al. "Population Pharmacokinetics of High-Dose, Prolonged-Infusion Cefepime in Adult Critically Ill Patients with Ventilator-Associated Pneumonia." Antimicrobial Agents and Chemotherapy 53, no. 4 (2009): 1476–81. http://dx.doi.org/10.1128/aac.01141-08.

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ABSTRACT A population pharmacokinetic model of cefepime was constructed from data from adult critical care patients with ventilator-associated pneumonia (VAP). A total of 32 patients treated with high-dose cefepime, 2 g every 8 h (3-h infusion) or a renal function-adjusted equivalent dose, were randomized into two groups—26 for the initial model and 6 for model validation. Serum samples of cefepime were collected at steady state. Nonparametric adaptive grid population modeling was employed using a two-compartment K slope pharmacokinetic model relating the elimination rate constant (K 10) to re
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Chen, M., A. N. Nafziger, G. L. Drusano, L. Ma, and J. S. Bertino. "Comparative Pharmacokinetics and Pharmacodynamic Target Attainment of Ertapenem in Normal-Weight, Obese, and Extremely Obese Adults." Antimicrobial Agents and Chemotherapy 50, no. 4 (2006): 1222–27. http://dx.doi.org/10.1128/aac.50.4.1222-1227.2006.

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ABSTRACT Little is known of the effects of obesity on ertapenem drug disposition and pharmacodynamics. Thirty healthy volunteers in three body mass index (BMI) groups (10 per group), normal weight (BMI, 18.5 to 24.9 kg/m2), class I-II obesity (BMI, 30 to 39.9 kg/m2), and class III obesity (BMI, ≥40 kg/m2), were administered a 1-g dose of ertapenem. Serum concentrations were obtained over 24 h. Population pharmacokinetic data were obtained using a nonparametric adaptive grid followed by Monte Carlo simulation to determine the probability of obtaining the free drug exposure targets of the time t
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Bulitta, J. B., M. Kinzig, C. B. Landersdorfer, U. Holzgrabe, U. Stephan, and F. Sörgel. "Comparable Population Pharmacokinetics and Pharmacodynamic Breakpoints of Cefpirome in Cystic Fibrosis Patients and Healthy Volunteers." Antimicrobial Agents and Chemotherapy 55, no. 6 (2011): 2927–36. http://dx.doi.org/10.1128/aac.01484-10.

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ABSTRACTCystic fibrosis (CF) patients are often reported to have higher clearances and larger volumes of distribution per kilogram of total body weight (WT) for beta-lactams than healthy volunteers. As pharmacokinetic (PK) data on cefpirome from studies of CF patients are lacking, we systematically compared its population PK and pharmacodynamic breakpoints for CF patients and healthy volunteers of similar body size. Twelve adult CF patients (median lean body mass [LBM] = 45.7 kg) and 12 healthy volunteers (LBM = 50.0 kg) received a single 10-min intravenous infusion of 2 g cefpirome. Plasma an
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