孕期第三 trimester 和产后的依非韦伦药代动力学。
Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum.
机构信息
Program for HIV Prevention and Treatment (IRD URI 174), Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
出版信息
J Acquir Immune Defic Syndr. 2012 Mar 1;59(3):245-52. doi: 10.1097/QAI.0b013e31823ff052.
BACKGROUND
The impact of pregnancy on efavirenz (EFV) pharmacokinetics is unknown.
METHODS
International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is an on-going, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving 600 mg EFV once daily as part of combination antiretroviral therapy. Intensive steady-state 24-hour blood sampling was performed during the third trimester and at 6-12 weeks postpartum. Maternal and umbilical cord blood samples were drawn at delivery. Pharmacokinetics targets were the estimated 10th percentile EFV area under the curve (AUC) in nonpregnant historical controls (40.0 mcg·hr(-1)·mL(-1)) and a trough concentration of 1 mcg/mL.
RESULTS
Twenty-five women were enrolled during the third trimester: median (range) age was 29.3 (18.9-42.9) years, weight 69.0 (40-130) kg, and gestational age 32.9 (30.1-38.7) weeks. Median (range) EFV AUC(0-24), C(max), and C(24 hours) were 55.4 mcg·hr(-1)·mL(-1) (13.5-220.3), 5.4 mcg/mL (1.9-12.2), and 1.6 mcg/mL (0.23-8.13), respectively. EFV AUC and C(max) did not differ during pregnancy and postpartum but C(24 hours) was lower during the third trimester (1.6 vs. 2.1 mcg/mL, P = 0.01). During the third trimester, 5 of 25 (20%) women had an EFV AUC below the target and 3 of 25 (12%) had a trough concentration below 1 mcg/mL. EFV cord blood/maternal concentration ratio was 0.49 (0.37-0.74). All women had a HIV-1 RNA viral load less than 400 copies per milliliter at delivery and 19 (76%) had a viral load below 50 copies per milliliter. One child was perinatally HIV infected. Three women were exposed to EFV throughout the first 6 weeks of pregnancy. EFV was well tolerated, and among the 25 infants, no congenital anomalies or newborn complications were reported.
CONCLUSIONS
Changes in EFV pharmacokinetics during pregnancy compared with postpartum are not sufficiently large enough to warrant a dose adjustment during pregnancy.
背景
妊娠对依非韦伦（EFV）药代动力学的影响尚不清楚。
方法
国际母婴儿科青少年艾滋病临床试验 P1026s 是一项正在进行的、前瞻性的、非盲的 HIV 感染孕妇抗逆转录病毒药代动力学研究，其中包括一组接受 600mg EFV 每日一次作为联合抗逆转录病毒治疗的一部分。在妊娠晚期和产后 6-12 周进行强化稳态 24 小时血样采集。在分娩时抽取母亲和脐带血样。药代动力学目标是未怀孕历史对照的估计第 10 百分位数 EFV 曲线下面积（AUC）（40.0 mcg·hr(-1)·mL(-1)）和谷浓度 1 mcg/mL。
结果
在妊娠晚期纳入 25 名妇女：中位（范围）年龄为 29.3（18.9-42.9）岁，体重 69.0（40-130）kg，孕龄 32.9（30.1-38.7）周。中位（范围）EFV AUC（0-24）、C(max)和 C(24 小时)分别为 55.4 mcg·hr(-1)·mL(-1)（13.5-220.3）、5.4 mcg/mL（1.9-12.2）和 1.6 mcg/mL（0.23-8.13）。EFV AUC 和 C(max)在妊娠和产后期间没有差异，但 C(24 小时)在妊娠晚期较低（1.6 与 2.1 mcg/mL，P=0.01）。在妊娠晚期，25 名妇女中有 5 名（20%）EFV AUC 低于目标值，25 名妇女中有 3 名（12%）谷浓度低于 1 mcg/mL。EFV 脐带血/母血浓度比为 0.49（0.37-0.74）。所有妇女在分娩时 HIV-1 RNA 病毒载量均低于每毫升 400 拷贝，19 名（76%）病毒载量低于每毫升 50 拷贝。有 1 名儿童围产期 HIV 感染。3 名妇女在整个妊娠前 6 周内接触 EFV。EFV 耐受性良好，在 25 名婴儿中，未报告先天性异常或新生儿并发症。
结论
与产后相比，EFV 药代动力学在妊娠期间的变化不够大，不需要在妊娠期间调整剂量。
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