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Academic literature on the topic 'AZT: Zidovudine Drug'
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Journal articles on the topic "AZT: Zidovudine Drug"
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Harilall, Sheri-Lee, Yahya E. Choonara, Girish Modi, et al. "Design and Pharmaceutical Evaluation of a Nano-Enabled Crosslinked Multipolymeric Scaffold for Prolonged Intracranial Release of Zidovudine." Journal of Pharmacy & Pharmaceutical Sciences 16, no. 3 (2013): 470. http://dx.doi.org/10.18433/j3r88k.
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Purpose. Nanomedicine explores and allows for the development of drug delivery devices with superior drug uptake, controlled release and fewer drug side-effects. This study explored the use of nanosystems to formulate an implantable drug delivery device capable of sustained zidovudine release over a prolonged period. Methods. Pectin and alginate nanoparticles were prepared by applying a salting out and controlled gelification approach, respectively. The nanoparticles were characterized by attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS) and were further evaluated for zidovudine (AZT) entrapment efficiency. Multipolymeric scaffolds were prepared by crosslinking carboxymethyl cellulose, polyethylene oxide and epsilon caprolactone for entrapment of zidovudine-loaded alginate nanoparticles to impart enhanced controlled release of zidovudine over the time period. Swelling and textural analysis were conducted on the scaffolds. Prepared scaffolds were treated with hydrochloric acid (HCl) to reduce the swelling of matrix in the hydrated environment thereby further controlling the drug release. Drug release studies in phosphate buffered saline (pH 7.4, 37°C) were undertaken on both zidovudine-loaded nanoparticles and native scaffolds containing alginate nanoparticles. Results. A higher AZT entrapment efficiency was observed in alginate nanoparticles. Biphasic release was observed with both nanoparticle formulations, exhibiting an initial burst release of drug within hours of exposure to PBS, followed by a constant release rate of AZT over the remaining 30 days of nanoparticle analysis. Exposure of the scaffolds to HCl served to reduce the drug release rate from the entrapped alginate nanoparticles and extended the AZT release up to 30 days. Conclusions. The crosslinked multipolymeric scaffold loaded with alginate nanoparticles and treated with 1% HCl showed the potential for prolonged delivery of zidovudine over a period of 30 days and therefore may be a potential candidate for use as an implantable device in treating Aids Dementia Complex.
 
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Khandazhinskaya, А. L., and E. A. Shirokova. "AZT 5’-Phosphonates: Achievements and Trends in the Treatment and Prevention of HIV Infection." Acta Naturae 5, no. 3 (2013): 54–61. http://dx.doi.org/10.32607/20758251-2013-5-3-54-61.
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Despite the numerous drawbacks, 3-azido-3-deoxythymidine (AZT, Zidovudine, Retrovir) remains one of the key drugs used in the treatment and prevention of HIV infection in both monotherapy and HAART. A strategy in searching for new effective and safe AZT agents among latent (depot) forms of AZT has yielded its first positive results. In particular, the sodium salt of AZT 5-H-phosphonate (Nikavir, phosphazide) has demonstrated clinical advantages over parent AZT: first and foremost, lower toxicity and better tolerability. It can be effectively used for the prevention of vertical transmission from mothers to babies and as an alternative drug for HIV-infected patients with low tolerance to Zidovudine. Preclinical studies of another phosphonate, AZT 5-aminocarbonylphosphonate, have demonstrated that it releases AZT when taken orally. Pharmacokinetic studies have shown a prolonged action potential. Based on the analysis of both toxicological and pharmacological data, AZT 5-aminocarbonylphosphonate has been recommended for clinical trials.
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Brown, Stacy D., Michael G. Bartlett, and Catherine A. White. "Pharmacokinetics of Intravenous Acyclovir, Zidovudine, and Acyclovir-Zidovudine in Pregnant Rats." Antimicrobial Agents and Chemotherapy 47, no. 3 (2003): 991–96. http://dx.doi.org/10.1128/aac.47.3.991-996.2003.
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ABSTRACT The pharmacokinetics and placental transfer of acyclovir and zidovudine monotherapies and acyclovir-zidovudine combination therapy were compared in the pregnant rat. Timed-pregnancy Sprague-Dawley rats were used for the study. Doses of 60 mg of each drug/kg of body weight in monotherapy and in combination therapy were given by intravenous bolus, and samples of maternal plasma, amniotic fluid, fetal tissue, and placental tissue were collected over a period of 8 h postdose. Concentrations of each drug in the various matrices were measured by high-performance liquid chromatography. All data were analyzed by using WinNonlin. A one-compartment model with first-order elimination was used to fit the AZT plasma data from the combination therapy rats, but the plasma data from the other groups were fit to a two-compartment model. Tissue data were analyzed by noncompartmental analysis to generate area-under-the-concentration-time-curve values. Implementation of the combination therapy altered the pharmacokinetics of each drug compared to its monotherapy pharmacokinetics. The combination of these two drugs may potentiate fetal and amniotic fluid exposures to each drug.
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Stankov, Metodi V., Reinhold E. Schmidt, and Georg M. N. Behrens. "Zidovudine Impairs Adipogenic Differentiation through Inhibition of Clonal Expansion." Antimicrobial Agents and Chemotherapy 52, no. 8 (2008): 2882–89. http://dx.doi.org/10.1128/aac.01505-07.
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ABSTRACT Lipoatrophy is a prevalent side effect of treatment with thymidine analogues. We wished to confine the time point of the antiadipogenic effect of zidovudine (AZT) during adipogenesis and to evaluate the antiproliferative effect of AZT on adipocyte homeostasis. We investigated the effects of AZT on adipogenesis in 3T3-F442A cells and studied their proliferation, differentiation, viability, and adiponectin expression. Cells were exposed to AZT (1 μM, 3 μM, 6 μM, and 180 μM), stavudine (d4T; 3 μM), or dideoxycytosine (ddC; 0.1 μM) for up to 15 days. Differentiation was assessed by real-time PCR and quantification of triglyceride accumulation. Proliferation and clonal expansion were determined by a [3H]thymidine incorporation assay. When they were induced to differentiate in the presence of AZT at the maximum concentration in plasma (C max) and lower concentrations, 3T3-F442A preadipocytes failed to accumulate cytoplasmic triacylglycerol and failed to express normal levels of the later adipogenic transcription factors, CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ. AZT exerted an inhibitory effect on the completion of the mitotic clonal expansion, which resulted in incomplete 3T3-F442A differentiation and, finally, a reduction in the level of adiponectin expression. In addition, AZT impaired the constitutive proliferation in murine and primary human subcutaneous preadipocytes. In contrast, incubation with d4T and ddC at the C max did not affect either preadipocyte proliferation or clonal expansion and differentiation. We conclude that the antiproliferative and antiadipogenetic effects of AZT on murine and primary human preadipocytes reveal the impact of the drug on fat tissue regeneration. These effects of the drug are expected to contribute to disturbed adipose tissue homeostasis and to be influenced by differential drug concentration and penetration in individual patients.
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Mariano, DOC, D. de Souza, DF Meinerz, et al. "The potential toxicological insights about the anti-HIV drug azidothymidine-derived monoselenides in human leukocytes: Toxicological insights of new selenium-azidothymidine analogs." Human & Experimental Toxicology 36, no. 9 (2016): 910–18. http://dx.doi.org/10.1177/0960327116674529.
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Acquired immunodeficiency syndrome (AIDS) is a worldwide disease characterized by impairments of immune function. AIDS can be associated with oxidative stress (OS) that can be linked to selenium (Se) deficiency. Se is fundamental for the synthesis of selenoproteins, such as glutathione peroxidase and thioredoxin reductase. These enzymes catalyze the decomposition of reactive oxygen species and contribute to maintain equilibrium in cell redox status. Literature data indicate that organoselenium compounds, such as ebselen and diphenyl diselenide, have antioxidant properties in vitro and in vivo models associated with OS. Nevertheless, selenocompounds can also react and oxidize thiols groups, inducing toxicity in mammals. Here, we tested the potential cytotoxic and genotoxic properties of six analogs of the prototypal anti-HIV drug azidothymidine (AZT) containing Se (5′-Se-(phenyl)zidovudine; 5′-Se-(1,3,5-trimethylphenyl)zidovudine; 5′-Se-(1-naphtyl)zidovudine; 5′-Se-(4-chlorophenyl)zidovudine) (C4); 5′-Se-(4-methylphenyl)zidovudine (C5); and 5′-(4-methylbenzoselenoate)zidovudine). C5 increased the rate of dithiothreitol oxidation (thiol oxidase activity) and C2-C4 and C6 (at 100 µM) increased DNA damage index (DI) in human leukocytes. Moreover, C5 (200 µM) decreased human leukocyte viability to about 50%. Taken together, these results indicated the low in vitro toxicity in human leukocytes of some Se-containing analogs of AZT.
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Jones, Jan L. "Drugs for AIDS/HIV:Assessing the Evidence." International Journal of Technology Assessment in Health Care 14, no. 3 (1998): 567–72. http://dx.doi.org/10.1017/s0266462300011533.
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AbstractThis article highlights factors that may cause bias in individual controlled trials or meta-analysis of zidovudine (AZT) in HIV disease. The overall benefit of AZT and antiretroviral drug combinations in the progression of HIV disease is probably greater than has been or can ever be shown in an ethical controlled trial.
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Driscoll, JS, DL Mayers, JP Bader, OS Weislow, DG Johns, and RW Buckheit. "2′-Fluoro-2′,3′-Dideoxyarabinosyladenine (F-ddA): Activity against Drug-Resistant Human Immunodeficiency Virus Strains and Clades A-E." Antiviral Chemistry and Chemotherapy 8, no. 2 (1997): 107–11. http://dx.doi.org/10.1177/095632029700800204.
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2′-Fluoro-2′,3′-dideoxyarabinosyladenine (F-ddA), an anti-human immunodeficiency virus (HIV) drug currently in clinical trial, was compared with zidovudine (AZT), ddl and ddC for anti-HIV activity and potency in HIV-1 strains both sensitive and resistant to zidovudine, ddl and non-nucleoside reverse transcriptase inhibitors. A variety of host cell systems [MT-2, MT-4, phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC)] was used. F-ddA was effective against each of the drug-resistant isolates, including the strain resistant to ddl, the other purine dideoxynucleoside evaluated in this study. The anti-HIV-1 activities of F-ddA and zidovudine were also determined against clades A-E in PHA-PBMCs. Although activities were similar, zidovudine was significantly more potent than F-ddA in the PHA-PBMC system.
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Wainberg, Mark A., Andre Dascal, and Jack Mendelson. "Anti-Retroviral Strategies for AIDS and Related Diseases." Canadian Journal of Infectious Diseases 2, no. 3 (1991): 121–28. http://dx.doi.org/10.1155/1991/487657.
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The replication cycle of human immunodeficiency virus type 1 (HIV-1) and other retroviruses consists of four stages: attachment of the virus to specific receptors on the cell surface; uncoating of the viral nucleic acid and conversion to DNA; production of viral RNA and proteins; and assembly and liberation of progeny virus from the cell. Each of these steps represents a potential target for antiviral chemotherapy. Combinations of drugs which act against different steps in the viral replication cycle might be expected to have synergistic potential. Zidovudine (AZT) is the most widely used drug to date for impeding the replication of HIV-1. Although AZT therapy has been reasonably successful, it has not been free from toxicity. In addition, there have been several reports of isolation of AZT-resistant variants of HIV-1.
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Christmas, James T., Bertis B. Little, Kraig A. Knoll, Roger E. Bawdon, and Larry C. Gilstrap III. "Teratogenic and Embryocidal Effects of Zidovudine (AZT) in Sprague-Dawley Rats." Infectious Diseases in Obstetrics and Gynecology 2, no. 5 (1995): 223–27. http://dx.doi.org/10.1155/s1064744995000068.
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Objective: The purpose of the present investigation was to analyze the effets of zidovudine on the postimplantation embryo and fetus.Methods: Pregnant Sprague-Dawley rats were given various doses (10 mg/kg, 30 mg/kg, 150 mg/kg) of zidovudine or saline by an endotracheal tube during the period of embryogenesis (days 6–8, 9–11, 6–11 postconception). The animals were sacrificed on days 18–19 of pregnancy, and their fetuses were removed by hysterotomy. Autopsies under low (15×) and high (40×) power light microscopy were performed on all fetuses.Results: There was no statistically significant difference among the groups with respect to maternal weight gain. There were more pregnancy resorptions in the group receiving high-dose zidovudine (150 mg/kg/day) throughout embryogenesis than in the control group (P = 0.001, respectively). Four major structural anomalies were noted among the 689 fetuses examined, but zidovudine was not associated with an increased frequency of congenital anomalies in rats when it was administered in doses similar to, 3-, and 15-fold higher than the regimen recommended for adult humans. The drug, however, was embryocidal in the high-dose group (P = 0.002).Conclusions: These findings are consistent with previous studies of preimplantation mouse embryos that demonstrated an embryocidal effect on preimplantation conceptuses. In summary, post-implantation embryonic zidovudine exposure was associated with significantly increased pregnancy losses (resorptions and intrauterine deaths).
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Bazzoli, C., H. Bénech, E. Rey, et al. "Joint Population Pharmacokinetic Analysis of Zidovudine, Lamivudine, and Their Active Intracellular Metabolites in HIV Patients." Antimicrobial Agents and Chemotherapy 55, no. 7 (2011): 3423–31. http://dx.doi.org/10.1128/aac.01487-10.
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ABSTRACTThe population pharmacokinetic parameters of zidovudine (AZT), lamivudine (3TC), and their active intracellular metabolites in 75 naïve HIV-infected patients receiving an oral combination of AZT and 3TC twice daily as part of their multitherapy treatment in the COPHAR2-ANRS 111 trial are described. Four blood samples per patient were taken after 2 weeks of treatment to measure drug concentrations at steady state. Plasma AZT and 3TC concentrations were measured in 73 patients, and among those, 62 patients had measurable intracellular AZT-TP and 3TC-TP concentrations. For each drug, a joint population pharmacokinetic model was developed and we investigated the influence of different covariates. We then studied correlations between the mean plasma and intracellular concentrations of each drug. A one-compartment model with first-order absorption and elimination best described the plasma AZT concentration, with an additional compartment for intracellular AZT-TP. A similar model but with zero-order absorption was found to adequately described concentrations of 3TC and its metabolite 3TC-TP. The half-lives of AZT and 3TC were 0.81 h (94.8%) and 2.97 h (39.2%), respectively, whereas the intracellular half-lives of AZT-TP and 3TC-TP were 10.73 h (69%) and 21.16 h (44%), respectively. We found particularly a gender effect on the apparent bioavailability of AZT, as well as on the mean plasma and intracellular concentrations of AZT, which were significantly higher in females than in males. Relationships between mean plasma drug and intracellular metabolite concentrations were also highlighted both for AZT and for 3TC. Simulation with the model of plasma and intracellular concentrations for once- versus twice-daily regimens suggested that a daily dosing regimen with double doses could be appropriate.