Ramanathan Raghu, Sivanesan Karthikeyan
1 Food and Hepatotoxicology Laboratory, Department of Pharmacology and Environmental Toxicology, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India.
J Pharm Pract. 2019 Feb;32(1):9-18. doi: 10.1177/0897190017735424. Epub 2017 Oct 10.
The HIV-infected patients are co-infected with many bacterial infections in which tuberculosis is most common found worldwide. These patients are often administered with combined therapy of anti-retroviral and anti-tubercular drugs which leads to several complications including hepatotoxicity or adverse drug interactions. The drug-drug interactions between the anti-retroviral and anti-tubercular drugs are not clearly defined and hence, this study was conducted to evaluate the pharmacokinetic drug-drug interactions of Zidovudine (AZT) with Isoniazid (INH) and its hepatotoxic metabolites. Seventy two rats were randomly divided into two major groups with their sub-groups each comprising 6 animals. The Group I received INH alone at a dose of 25 mg/kg; b.w and Group II received AZT (50 mg/kg; b.w) along with INH orally. Pharmacokinetic studies of INH and its metabolites i.e., acetyl hydrazine (ACHY) and hydrazine (HYD) shows that INH and ACHY attains maximum plasma concentration ( C) within 30 minutes and HYD attains C at 1 hour after INH administration and all these analytes disappear from plasma within 4 hours. Pharmacokinetic studies also revealed that AZT treatment did not showed any drug-drug interactions and have no effect on the T, plasma clearance, AUC, C and T of INH and its hepatotoxic metabolites.
感染艾滋病毒的患者常合并多种细菌感染，其中结核病在全球最为常见。这些患者通常接受抗逆转录病毒药物和抗结核药物的联合治疗，这会导致多种并发症，包括肝毒性或药物不良反应。抗逆转录病毒药物和抗结核药物之间的药物相互作用尚不明确，因此，本研究旨在评估齐多夫定（AZT）与异烟肼（INH）及其肝毒性代谢产物的药代动力学药物相互作用。72只大鼠被随机分为两大组，每组再分为若干亚组，每组6只动物。第一组单独接受剂量为25mg/kg体重的异烟肼；第二组口服齐多夫定（50mg/kg体重）和异烟肼。异烟肼及其代谢产物即乙酰肼（ACHY）和肼（HYD）的药代动力学研究表明，异烟肼和乙酰肼在给药后30分钟内达到最大血浆浓度（C），肼在给药后1小时达到C，所有这些分析物在4小时内从血浆中消失。药代动力学研究还表明，齐多夫定治疗未显示任何药物相互作用，对异烟肼及其肝毒性代谢产物的T、血浆清除率、AUC、C和T均无影响。
