拉米夫定、司他夫定和奈韦拉平的仿制药与原研药制剂在感染艾滋病毒的马拉维儿童中的药代动力学
Pharmacokinetics of generic and trade formulations of lamivudine, stavudine and nevirapine in HIV-infected Malawian children.
作者信息
Corbett Amanda H, Hosseinipour Mina C, Nyirenda Jean, Kanyama Cecelia, Rezk Naser L, Mkupani Pax, Sichali Dorothy, Tien Hsiao, Kashuba Angela Dm, Mwansambo Charles, Weigel Ralf, Kazembe Peter
机构信息
University of North Carolina Schools of Pharmacy, Medicine and Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
出版信息
Antivir Ther. 2010;15(1):83-90. doi: 10.3851/IMP1488.
BACKGROUND
The aim of this study was to evaluate the pharmacokinetics of lamivudine (3TC), stavudine (d4T) and nevirapine (NVP) in HIV-infected Malawian children receiving quartered tablet multiples of Triomune 40 (generic tablet [GT]) compared with individual generic liquid (GL) and trade liquid (TL).
METHODS
This was a prospective randomized three-way crossover study. Patients (8-<12 kg, 18-<22 kg or 28-<32 kg body weight) taking Triomune 40 were recruited and randomized to receive GT twice daily (one-quarter, one-half or three-quarter tablets using Malawi treatment guidelines), GL twice daily (in the equivalent dose of GT) or TL twice daily (dosed using weight and age from US Department of Health and Human Services paediatric treatment guidelines). After 10 days of one formulation, 6-h pharmacokinetic sampling was performed, and patients were crossed over to subsequent formulations. Baseline concentration (C(0 h)), area under the curve (AUC)(0-6 h), maximum plasma concentration (C(max)) and time to C(max) were generated for each antiretroviral treatment.
RESULTS
A total of 7 males and 11 females (6 in each GT dosing group) with a median (range) age of 7.2 years (1.3-13.6), weight of 19 kg (9.0-30.5) and height of 109 cm (75-132) were recruited. Combining all patients, no difference in pharmacokinetics was noted among the formulations for all drugs. However, patients in the one-quarter GT dosing group (8-<12 kg) had lower 3TC exposures than with the GL or TL (3TC AUC(0-6 h) 1,102, 1,720 and 2,060 h*ng/ml, respectively; P<0.005) and had more subtherapeutic NVP C(0 h) (10 of 13 occasions versus the one-half and three-quarter tablet groups). Compared with Western paediatric cohorts, Malawians had concentrations 30-40% lower for 3TC and d4T and 50% higher for NVP.
CONCLUSIONS
Quartered multiples of Triomune 40 are appropriate for children 18-<22 kg and 28-<32 kg in weight; however, alternative formulations are suggested in children weighing 8-<12 kg.
背景
本研究旨在评估与单独的通用液体剂型（GL）和市售液体剂型（TL）相比，接受四分片装的三联免疫40（通用片剂[GT]）的HIV感染马拉维儿童中拉米夫定（3TC）、司他夫定（d4T）和奈韦拉平（NVP）的药代动力学。
方法
这是一项前瞻性随机三交叉研究。招募服用三联免疫40的患者（体重8 - <12 kg、18 - <22 kg或28 - <32 kg），并随机分为每日两次接受GT（按照马拉维治疗指南服用四分之一、二分之一或四分之三片）、每日两次接受GL（与GT等效剂量）或每日两次接受TL（根据美国卫生与公众服务部儿科治疗指南按体重和年龄给药）。一种剂型服用10天后，进行6小时药代动力学采样，然后患者交叉换用后续剂型。对每种抗逆转录病毒治疗生成基线浓度（C(0 h)）、曲线下面积（AUC）(0 - 6 h)、最大血浆浓度（C(max)）和达峰时间。
结果
共招募了7名男性和11名女性（每个GT给药组6名），中位（范围）年龄为7.2岁（1.3 - 13.6岁），体重19 kg（9.0 - 30.5 kg），身高109 cm（75 - 132 cm）。综合所有患者，所有药物在各剂型间药代动力学无差异。然而，四分之一GT给药组（8 - <12 kg）的患者3TC暴露量低于GL或TL（3TC的AUC(0 - 6 h)分别为1,102、1,720和2,060 h*ng/ml；P<0.005），且NVP的C(0 h)低于治疗水平的情况更多（13次中有10次，而二分之一片和四分之三片组较少）。与西方儿科队列相比，马拉维人的3TC和d4T浓度低30 - 40%，NVP浓度高50%。
结论
三联免疫40的四分片装适合体重18 - <22 kg和28 - <32 kg的儿童；然而，对于体重8 - <12 kg的儿童，建议使用其他剂型。
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