ORIGINAL ARTICLE Development and validation of a normal-phase HPTLC method for the simultaneous analysis of Lamivudine and Zidovudine in fixed-dose combination tablets

Simultaneous quantification of Lamivudine and Zidovudine in tablets by HPTLC method was developed and validated.The chromatograms were developed using a mobile phase of toluene:ethyl acetate:methanol (4:4:2,v/v/v) on pre-coated plate of silica gel GF aluminum TLC plate and quantified by densitometric absorbance mode at 276 nm.The R f values were 0.4170.03 and 0.6070.04 for Lamivudine and Zidovudine,respectively.The linearity of the method was found to be within the concentration range of 50 250 ng/spot for Lamivudine and for Zidovudine,it was 100 500 ng/spot.The lower limits of detection and quantification were 2.23 ng/spot and 7.90 ng/spot for Lamivudine and 2.90 ng/spot and 8.85 ng/spot for Zidovudine.The method was also validated for precision,specificity and recovery.This developed method was used to analyze fixed-dose tablets (Duovir,Cipla Ltd) samples of Lamivudine and Zidovudine.

Determination of the Antiretroviral Drug Zidovudine in Diluted Alkaline Electrolyte by Adsorptive Stripping Voltammetry at the Mercury Film Electrode

This paper describes a stripping method for the determination of zidovudine at the submicromolar concentration levels. This method is based on the controlled adsorptive accumulation of zidovudine at the thin-film mercury electrode, followed by a linear-sweep stripping voltammetry measurement of the surface species. Optimal experimental conditions include a NaOH solution of 2.0 × 10–3 mol●L–1 (sup-porting electrolyte), an accumulation potential of –0.30 V and a scan rate of 100 mV?s–1. The response of zidovudine is linear over the concentration range 0.01 - 0.08 ppm. After an accumulation time of 5 minutes, the detection limit was found to be 0.67 ppb (2.5 × 10–9 mol●L–1). More convenient methods to measure zidovudine concentration in the presence of the didanosine, acyclovir, nevirapine, lamivudine, and efavirenz, were also investigated. The presence of zidovudine together with ATP or ssDNA demonstrates the utility of this method.

Trizivir (Abacavir/Lamivudine/Zidovudine) plus Lopinavir/Ritonavir Induction Therapy Followed by Trizivir-Alone Maintenance for HIV-1-Infected Patients: A 96-Week Pilot Treatment Simplification Study

Objective: The purpose of this study was to investigate whether switching HIV-infected patients stabilized on Trizivir (abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg) plus lopinavir/ritonavir 400 mg/100mg twice daily to Trizivir alone affects clinical efficacy and tolerability. Methods: This phase 4, open-label, pilot study was conducted over 96 weeks in 23 antiretroviral-na?ve, HIV-infected patients. Initially, these patients received induction therapy with Trizivir plus lopinavir/ritonavir 400 mg/100mg twice daily. Patients who achieved a viral load 3. Nineteen patients completed induction;of the four who did not, three were lost to follow-up and one withdrew due to gastrointestinal adverse events. In 14 induction completers who had viral load measurements taken at week 48, intent-to-treat: observed analysis showed a week 48 viral load 3 higher than the baseline count. Twelve patients completed the subsequent 48-week Trizivir-alone maintenance phase, of whom 11 (92%) achieved viral loads of both 3 above baseline. Trizivir-only maintenance was associated with fewer adverse events than the Trizivir-lopinavir/ritonavir induction phase and with improvement in total cholesterol, LDL-cholesterol, and triglycerides. Conclusions: Trizivir-alone maintenance after Trizivir-lopinavir/ritonavir induction maintained virologic and CD4+ cell response, and was associated with an improved adverse event and lipid profile.

An antiretroviral regimen containing 6 months of stavudine followed by long-term zidovudine for first-fine HIV therapy is optimal in resource-limited settings： a prospective, multicenter study in China

Background An zidovudine （AZT）-substitution regimen containing 24-week stavudine （d4T） followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resourcelimited settings.However,evidence is scarce.This study aims to assess the efficacy and safety of AZT-substitution regimen,aiming to find a regimen with better efficacy,less adverse events,and more affordability in resource-limited settings.Methods This prospective,multicenter study enrolled 499 （190 on d4T regimen,172 on AZT regimen,and 137 on AZT-substitution regimen） HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011.Lamivudine （3TC） and either nevirapine （NVP） or efavirenz （EFV） were the other two drugs in the antiretroviral regimens.Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4,12,24,36,48,60,72,84,and 96.Results In terms of hematological adverse effects,AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group.In comparison with AZT-substitution group,AZT group was associated with higher risk of developing anemia （adjusted hazard ratio （aHR）for anemia ≥ grade Ⅱ,8.44,95％ CI 1.81-39.46） and neutropenia （aHR for neutropenia ≥ grade Ⅱ,1.86,95％ CI 1.19-2.93）.The prevalence of lipodystrophy in d4T group was 19.5％,while that in AZT-substitution group was zero.As to antiretroviral efficacy,these three groups showed no differences.Conclusion AZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.

Steady-state pharmacokinetics of zidovudine in Chinese HIV-infected patients

Background The pharmacokinetics of zidovudine （AZT） are possibly influenced by weight, age, sex, liver and renal functions, severity of disease, and ethnicity. Currently, little information is available on the steady-state pharmacokinetics of AZT in Chinese HIV-infected patients. The current study aimed to characterize the steady-state pharmacokinetics of AZT in a Chinese set-up. Methods Eleven Chinese HIV-infected patients were involved in the steady-state pharmacokinetic study. In total, 300 mg of AZT, as a part of combination therapy, was given to patients, and serial blood samples were collected for 12 hours. The samples were measured by a high-performance liquid chromatography （HPLC） assay, and the results were analyzed by both the non-compartment model and the one-compartment model. Results The Cmax of AZT in Chinese patients was higher than that in non-Asian patients. The half-life of AZT, analyzed by the non-compartment model （P=-0.02）, in male patients （（1.02±0.22） hours） was shorter than that of AZT in female patients （（1.55±0.29） hours）. The AZT clearance, analyzed by the one-compartment model （P=0.045）, in male patients （（262.60±28.13） L/h） was higher than that in female patients （（195.85±60.51） L/h）. Conclusion The present study provides valuable information for the clinical practice of AZT-based highly active antiretroviral therapy in a Chinese set-up.

Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites

Zidovudine (AZT), the first drug approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection, is metabolized in the host cells to 5'-AZT triphosphate (AZT-TP) which inhibits HIV reverse transcriptase. As the pharmacokinetics of AZT and its phosphorylated metabolites in human peripheral blood mononuclear cells (hPBMCs) is limited, the aim of this study was to determine the pharmacokinetic parameters of AZT and its phosphorylated metabolites in hPBMCs from 12 healthy Chinese male subjects after a single oral dose of 600 mg of AZT. Blood samples were collected prior to drug administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 10 h after drug administration. Mononuclear cells collected by Ficoll-Hypaque density gradient centrifugation were used for determination of AZT and metabolites [AZT monophosphate (AZT-MP), AZT diphosphate (AZT-DP) and AZT-TP] and the plasma was used to evaluate the pharmacokinetics of AZT. Plasma concentration of AZT peaked within 0.583 h and intracellular concentrations of AZT, AZT-MP, AZT-DP and AZT-TP peaked within 1.083, 1.500, 1.417 and 1.583 h, respectively. AZT in plasma was eliminated rapidly with t(1/2) of 2.022 h, and AZT-MP, AZT-DP and AZT-TP were eliminated with t(1/2) of 13.428, 8.285 and 4.240 h, respectively. The plasma concentration of the phosphorylated metabolites was not quantifiable. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

Simultaneous quantitation of lamivudine,zidovudine and nevirapine in human plasma by liquid chromatography-tandem mass spectrometry and application to a pharmacokinetic study

A rapid and sensitive LC-MS/MS method for the simultaneous quantitation of lamivudine,zidovudine and nevirapine in human plasma using abacavir as internal standard has been developed and validated.The analytes and IS were extracted from plasma by solid phase extraction using Oasis HLB cartridges and separated on a Hypurity Advance C18 column using a mixture of acetonitrile:0.1% formic acid(76:24,v/v)at a flow rate of 0.8 mL/min.Detection involved an API-4000 LC MS/MS with electrospray ionization in the positive ion mode and multiple-reaction monitoring for analysis.The method was validated according to FDA guidelines and shown to provide intra-and inter-day precision and accuracy within acceptable limits in a run time of only 3.5 min.The method was sucessfully applied to a pharmacokinetic study involving a single oral administration of a combination tablet to human male volunteers.

Determination of zidovudine using anion exchange chromatography with integrated pulsed amperometric detection

A rapid and practical method for direct detection of zidovudine in high performance anion exchange chromatography （HPAEC） has been developed with integrated pulsed amperometric detection （IPAD）. Dionex AS18 （250mm × 2mm） and AG18 （50 mm× 2 mm） columns and 11 mmol/L NaOH solution were used for separation. Multi-step potential waveform parameters were optimized to maximize the signal-to-noise ratio （S/N）. Utilizing an optimized waveform, the repeatability （intra-day） precision and intermediate （inter-day） precision are obtained with relative standard deviation （RSD） of 1.88, 2.27, respectively. The limit of quantification （LOQ） and limit of detection （LOD） were found to be 9.70, 3.0 ng/mL, respectively, with correlation coefficients of 0.9992 over concentration range 0.01-10 μg/mL. The present method was successfully applied to the determination of zidovudine in human plasma. The recoveries of plasma sample spiked by 0.7 μg/mL, 2.7 μg/mL obtained were 95.3-101.5%, with relative standard deviation （RSD） of 2.54%, 2.21%, respectively.

Necrotising stomatitis as a presenting symptom of HIV

Background: Necrotising Stomatitis is an uncommon oral infection associated with diminished systemic resistance (immunocompromised state) including HIV infection. Significant predisposing factors include poor oral hygiene, unusual life stress, recent illness (e.g. Measles), malnutrition, smoking and even inade- quate sleep. It occurs commonly in developing na-tions with poor living conditions. Objective: To present a case of severe Necrotising Stomatitis in a previously undiagnosed HIV Seropositive patient. Patient and method: This case report describes severe, rapidly spreading necrotising stomatitis in a 35 years old lady, the condition which led to her being diagnosed with HIV. The treatment modalities, challenges of man-agement and the differential diagnosis were discussed. Result: During the course of her management, pa-tient’s oral condition improved. However, later re-currence was seen due to severe anaemia caused by malnutrition and aggravated by Zidovudine antiret-roviral drug. Conclusions: There is need for interdis-ciplinary interactions between the dentists and the physicians managing HIV patients, to allow effective management and afford patient the best treatment.

Melanonychia in Patients Infected with Human Immunodeficiency Virus Original Communication

This study examined whether melanonychia was more prevalent in 1) HIV positive individuals compared to HIV negative persons, 2) HIV positives exposed to zidovudine and/or stavudine and 3) those with darker skin pigmentation. Procedures. 267 HIV positive and 273 HIV negative patients were examined for presence or absence of melanonychia and level of skin pigmentation using the Fitzgerald scale. Pharmacy records were examined for determining exposure to zidovudine or stavudine. Chi square, odds ratios and logistic regression were used to examine the study questions Main Findings. Melanonychia appeared in 49.1% of 267 HIV positive and 21.8% of 273 HIV negative subjects. Adjusting for skin pigmentation, HIV positives were 4.1 times more likely to have melanonychia than HIV negatives. Melanonychia was present in 54% of those receiving zidovudine and in 42% of those receiving stavudine (OR = 2.73, p = 0.05). In a multivariate model in HIV positives which included skin type, prescription of zidovudine and/or Stavudine, only dark skin (OR = 14.62, p < 0.001) and zidovudine (OR = 2.65, p < 0.03) were significant. Principal Conclusions. HIV infected persons are prone to melanonychia. This is more frequent in darker skinned persons and is enhanced in those exposed to zidovudine.

齐多夫定注射液制剂处方及工艺的研究

目的对齐多夫定(Z idovud ine)注射液制剂处方及工艺进行研究。方法参阅相关文献,并根据齐多夫定本身理化性质和同类药物的注射剂处方设计要求,通过试验,对齐多夫定注射液制剂处方及工艺进行筛远。结果筛选出了符合注射剂质量要求的齐多夫定注射液处方及工艺。结论经过实验筛选确定了齐多夫定(Z idovud ine)注射液制剂处方及工艺。