Nevirapine plasma concentrations are still detectable after more than 2 weeks in the majority of women receiving single-dose nevirapine - Implications for intervention studies
Nevirapine plasma concentrations are still detectable after more than 2 weeks in the majority of women receiving single-dose nevirapine - Implications for intervention studies
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DOI：
10.1097/01.qai.0000167154.37357.f9
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发表时间：
2005-08-01
影响因子：
3.6
通讯作者：
Burger, DM
中科院分区：
文献类型：
--
作者：
Muro, E;Droste, JAH;Burger, DM
背景：单剂量奈韦拉平是减少围产期 HIV-1 传播的一种极具成本效益的策略。其主要缺点是 20% 至 30% 的女性对奈韦拉平产生耐药性，这可能是由于奈韦拉平的消除半衰期较长。为了制定干预策略，了解接受单剂量奈韦拉平的女性奈韦拉平半衰期的患者间变异性非常重要。方法：HIV阴性、健康、非怀孕的荷兰女性符合本研究的资格。受试者接受单剂量奈韦拉平 200 毫克后，每周采集两次血液样本，测量奈韦拉平浓度，总共 21 天。奈韦拉平血浆水平通过经过验证的高效液相色谱法测定，定量下限为 0.15 mg/L。主要终点是奈韦拉平浓度无法检测到的第一个样本。结果：44 名受试者参与。中位年龄、身高和体重（四分位距）分别为 26（21-33）岁、1.72（1.68-1.75）米和 64（59-75）公斤。奈韦拉平的中位消除半衰期为 56.7 小时，范围为 25.6 至 164 小时。 4 名受试者首次检测不到奈韦拉平血浆浓度的时间为 10 天，12 名受试者为 14 天，12 名受试者为 17 天，9 名受试者为 21 天。在其余 7 名受试者中，在第 21 天（采样的最后一天）仍可检测到奈韦拉平。达到不可检测的奈韦拉平血浆浓度的时间受口服避孕药使用的影响，但不受年龄、身高、体重、体表面积、饮酒或吸烟的影响。 结论：大多数接受单次 200 mg 奈韦拉平剂量的女性在 2 周以上后仍具有可检测到的奈韦拉平血浆浓度。该信息对于设计干预研究以防止奈韦拉平耐药性的发展非常有价值。
Background: Single-dose nevirapine is a highly cost-effective strategy to reduce perinatal HIV-1 transmission. Its major disadvantage is the selection of nevirapine resistance in 20% to 30% of women, probably attributable to the long elimination half-life of nevirapine. To develop intervention strategies, it is important to know the interpatient variability in nevirapine half-life in women receiving a single dose of nevirapine.Methods: HIV-negative, healthy, nonpregnant Dutch women were eligible for this study After administration of a single 200-mg dose of nevirapine to the subjects, blood was sampled for measurement of nevirapine twice a week for a total of 21 days. Nevirapine plasma levels were determined by a validated high-performance liquid chromatography method with a lower limit of quantification of 0.15 mg/L. The primary end point was the first sample with an undetectable nevirapine concentration.Results: Forty-four subjects participated. The median age, height, and body weight (interquartile range) were 26 (21-33) years, 1.72 (1.68-1.75) m, and 64 (59-75) kg, respectively. The median elimination half-life of nevirapine was 56.7 hours, with a range of 25.6 to 164 hours. The time to the first undetectable nevirapine plasma concentration was 10 days in 4 subjects, 14 days in 12 subjects, 17 days in 12 subjects, and 21 days in 9 subjects. In the remaining 7 subjects, nevirapine was still detectable on day 21, the last day of sampling. Time to an undetectable nevirapine plasma concentration was influenced by oral contraceptive use but not by age, height, body weight, body surface area, alcohol use, or smoking.Conclusions: Most women who received a single 200-mg nevirapme dose still had detectable plasma concentrations of nevirapine after more than 2 weeks. This information is valuable for designing intervention studies to prevent the development of nevirapine resistance.