Muro Eva, Droste Jacqueline A H, Hofstede Hadewych Ter, Bosch Marjolein, Dolmans Wil, Burger David M
Kilimanjaro Christian Medical College, Tumaini University, Moshe, Tanzania.
J Acquir Immune Defic Syndr. 2005 Aug 1;39(4):419-21. doi: 10.1097/01.qai.0000167154.37357.f9.
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.
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.
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.
Most women who received a single 200-mg nevirapine 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.
单剂量奈韦拉平是降低围产期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%的女性会出现奈韦拉平耐药，这可能归因于奈韦拉平较长的消除半衰期。为制定干预策略，了解接受单剂量奈韦拉平的女性中奈韦拉平半衰期的个体间差异很重要。
HIV阴性、健康、未怀孕的荷兰女性符合本研究条件。给受试者单次服用200毫克奈韦拉平后，每周采集两次血液样本以检测奈韦拉平，共采集21天。通过经过验证的高效液相色谱法测定奈韦拉平血浆水平，定量下限为0.15毫克/升。主要终点是奈韦拉平浓度不可检测的首个样本。
44名受试者参与研究。年龄、身高和体重的中位数（四分位间距）分别为26（21 - 33）岁、1.72（1.68 - 1.75）米和64（59 - 75）千克。奈韦拉平的消除半衰期中位数为56.7小时，范围为25.6至164小时。4名受试者在10天时、12名受试者在14天时、12名受试者在17天时以及9名受试者在21天时首次出现奈韦拉平血浆浓度不可检测。在其余7名受试者中，在采样的最后一天即第21天时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情况影响，但不受年龄、身高、体重、体表面积、饮酒或吸烟影响。
大多数接受单次200毫克奈韦拉平剂量的女性在两周多后血浆中仍可检测到奈韦拉平浓度。该信息对于设计预防奈韦拉平耐药的干预研究很有价值。
