一项单剂量、随机、开放标签、两期交叉生物等效性研究，研究对象为健康成年男性志愿者，使用的药物为固定剂量的儿科用拉米夫定40毫克、奈韦拉平70毫克和司他夫定10毫克片剂与个体化液体制剂的口服混悬液。

A single-dose, randomized, open-label, two-period crossover bioequivalence study of a fixed-dose pediatric combination of lamivudine 40-mg, nevirapine 70-mg, and stavudine 10-mg tablet for oral suspension with individual liquid formulations in healthy adult male volunteers.

作者信息

Monif Tausif, Rao Thudi Nageshwar, Koundinya Tippabhotla Sudhakar, Khuroo Arshad, Marwah Amit, Kumar Shrivastav Vikesh, Tandon Monika, Raghuvanshi Rajeev, Biswal Shibadas

机构信息

Department of Clinical Pharmacology and Pharmacokinetics, Ranbaxy Laboratories Ltd., Plot No. 20, Sector-18, Udyog Vihar Industrial Area, Gurgaon 122 015, Haryana, India.

出版信息

Clin Ther. 2007 Dec;29(12):2677-84. doi: 10.1016/j.clinthera.2007.12.028.

DOI:10.1016/j.clinthera.2007.12.028

PMID:18201583

Abstract

BACKGROUND

Because of the lack of suitable pediatric antiretroviral (ARV) agents, adult fixed-dose ARVs are commonly used in children. This practice poses concerns about dose inaccuracy, which may lead to resistance or toxicity.

OBJECTIVE

The objective of the present study was to evaluate the bioequivalence of a new pediatric fixed-dose combination (FDC) ARV tablet for oral suspension as compared with individual liquid formulations.

METHODS

The FDC ARV tablet for oral suspension contained lamivudine 40 mg, nevirapine 70 mg, and stavudine 10 mg. This formulation was compared with 4 mL of lamivudine 10 mg/mL, 7 mL of nevirapine 50 mg/5 mL, and 10 mL of stavudine 1 mg/mL. This was an open-label, balanced, randomized, 2-treatment, 2-period, 2-sequence, single-dose crossover study in 36 Indian male volunteers under fasting conditions. Blood samples were collected before dosing and at 0.167, 0.25, 0.333, 0.5, 0.667, 0.833, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours after dosing in each period.

RESULTS

The mean (SD) age, weight, and height of the Indian volunteers were 24.78 (5.31) years (range, 18-38 years), 57.06 (8.59) kg (range, 45-77 kg), and 165.14 (5.34) cm (range, 156-176 cm), respectively. The mean (SD) values for T(max), C(max), and AUC(0-t) for the FDC and the individual liquid formulations, respectively, were as follows: lamivudine, 0.71 (0.22) and 0.89 (0.50) hour, 594 (167) and 514 (139) ng/mL, 2382 (617) and 2227 (666) ng /mL per hour; nevirapine, 1.7 (1.1) and 2.5 (1.2) hours, 1248 (275) and 1185 (238) ng/mL, 70,372 (14,869) and 71,278 (17,435) ng/ mL per hour; and stavudine, 0.44 (0.11) and 0.43 (0.11) hour, 348 (82) and 395 (107) ng/mL, and 576 (113) and 631 (142) ng/mL per hour. The ratios and 90% CIs for the least-squares mean Cmax and AUC values were found to be within the prespecified range of 80% to 125% for each component.

CONCLUSION

The FDC pediatric formulation of lamivudine, nevirapine, and stavudine was bioequivalent to the individual liquid formulations in these fasting, healthy Indian men.

摘要

背景

由于缺乏合适的儿科抗逆转录病毒（ARV）药物，成人固定剂量抗逆转录病毒药物常用于儿童。这种做法引发了对剂量不准确的担忧，这可能导致耐药性或毒性。

目的

本研究的目的是评估一种新型儿科固定剂量复方（FDC）抗逆转录病毒口服混悬剂片剂与单独液体制剂的生物等效性。

方法

该FDC抗逆转录病毒口服混悬剂片剂含有40毫克拉米夫定、70毫克奈韦拉平和10毫克司他夫定。将该制剂与4毫升10毫克/毫升的拉米夫定、7毫升50毫克/5毫升的奈韦拉平和10毫升1毫克/毫升的司他夫定进行比较。这是一项在36名印度男性志愿者中进行的开放标签、均衡、随机、双治疗、双周期、双序列、单剂量交叉研究，研究在禁食条件下进行。在每个周期给药前以及给药后0.167、0.25、0.333、0.5、0.667、0.833、1、1.25、1.5、2、2.5、3、3.5、4、4.5、5、6、12、16、24、36、48、72、96、120、144、168和192小时采集血样。

结果

印度志愿者的平均（标准差）年龄、体重和身高分别为24.78（5.31）岁（范围18 - 38岁）、57.06（8.59）千克（范围45 - 77千克）和165.14（5.34）厘米（范围156 - 176厘米）。FDC和单独液体制剂的T(max)、C(max)和AUC(0 - t)的平均（标准差）值分别如下：拉米夫定，0.71（0.22）和0.89（0.50）小时，594（167）和514（139）纳克/毫升，2382（617）和2227（666）纳克/毫升·小时；奈韦拉平，1.7（1.1）和2.5（1.2）小时，1248（275）和1185（238）纳克/毫升，70372（14869）和71278（17435）纳克/毫升·小时；司他夫定，0.44（0.11）和0.43（0.11）小时，348（82）和395（107）纳克/毫升，以及576（113）和631（142）纳克/毫升·小时。发现各组分的最小二乘均值Cmax和AUC值的比值及90%置信区间在预先规定的80%至125%范围内。