Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, CA, USA.
HIV Med. 2012 Apr;13(4):226-35. doi: 10.1111/j.1468-1293.2011.00965.x. Epub 2011 Nov 30.
The aim of the study was to describe emtricitabine pharmacokinetics during pregnancy and postpartum.
The International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT), formerly Pediatric AIDS Clinical Trials Group (PACTG), study P1026s is a prospective pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including a cohort taking emtricitabine 200 mg once daily. Intensive steady-state 24-hour emtricitabine pharmacokinetic profiles were performed during the third trimester and 6-12 weeks postpartum, and on maternal and umbilical cord blood samples collected at delivery. Emtricitabine was measured by liquid chromatography-mass spectrometry with a quantification limit of 0.0118 mg/L. The target emtricitabine area under the concentration versus time curve, from time 0 to 24 hours post dose (AUC(0-24) ), was ≥7 mg h/L (≤30% reduction from the typical AUC of 10 mg h/L in nonpregnant historical controls). Third-trimester and postpartum pharmacokinetics were compared within subjects.
Twenty-six women had pharmacokinetics assessed during the third trimester (median 35 weeks of gestation) and 22 postpartum (median 8 weeks postpartum). Mean [90% confidence interval (CI)] emtricitabine pharmacokinetic parameters during the third trimester vs. postpartum were, respectively: AUC: 8.0 (7.1-8.9) vs. 9.7 (8.6-10.9) mg h/L (P = 0.072); apparent clearance (CL/F): 25.0 (22.6-28.3) vs. 20.6 (18.4-23.2) L/h (P = 0.025); 24 hour post dose concentration (C(24) ): 0.058 (0.037-0.063) vs. 0.085 (0.070-0.010) mg/L (P = 0.006). The mean cord:maternal ratio was 1.2 (90% CI 1.0-1.5). The viral load was <400 HIV-1 RNA copies/mL in 24 of 26 women in the third trimester, in 24 of 26 at delivery, and in 15 of 19 postpartum. Within-subject comparisons demonstrated significantly higher CL/F and significantly lower C(24) during pregnancy; however, the C(24) was well above the inhibitory concentration 50%, or drug concentration that suppresses viral replication by half (IC(50) ) in all subjects.
While we found higher emtricitabine CL/F and lower C(24) and AUC during pregnancy compared with postpartum, these changes were not sufficiently large to warrant dose adjustment during pregnancy. Umbilical cord blood concentrations were similar to maternal concentrations.
本研究旨在描述怀孕期间和产后的恩曲他滨药代动力学。
国际母婴儿科艾滋病临床试验（IMPAACT），前身为儿科艾滋病临床试验组（PACTG），研究 P1026s 是一项针对接受抗逆转录病毒治疗的 HIV 感染孕妇的前瞻性药代动力学研究，包括一个接受恩曲他滨 200mg 每日一次的队列。在妊娠晚期和产后 6-12 周进行强化稳态 24 小时恩曲他滨药代动力学分析，并在分娩时采集母亲和脐带血样本。恩曲他滨通过液相色谱-质谱法进行测量，定量下限为 0.0118mg/L。从时间 0 到 24 小时的恩曲他滨浓度-时间曲线下面积（AUC(0-24) ）目标值为≥7mg·h/L（与非妊娠历史对照的典型 AUC 值 10mg·h/L相比，降低≤30%）。对同一受试者的妊娠晚期和产后药代动力学进行比较。
26 名女性在妊娠晚期（中位 35 孕周）和 22 名女性在产后（中位产后 8 周）进行了药代动力学评估。与产后相比，妊娠晚期的平均[90%置信区间（CI）]恩曲他滨药代动力学参数分别为：AUC：8.0（7.1-8.9）比 9.7（8.6-10.9）mg·h/L（P=0.072）；表观清除率（CL/F）：25.0（22.6-28.3）比 20.6（18.4-23.2）L/h（P=0.025）；24 小时后浓度（C(24) ）：0.058（0.037-0.063）比 0.085（0.070-0.010）mg/L（P=0.006）。脐带：母体比值的均值为 1.2（90%CI 1.0-1.5）。在妊娠晚期，26 名女性中有 24 名（24/26，92.3%）、分娩时 26 名中有 24 名（24/26，92.3%）、产后 19 名中有 15 名（15/19，78.9%）的病毒载量<400 HIV-1 RNA 拷贝/mL。个体内比较显示，妊娠期间恩曲他滨 CL/F 显著升高，C(24) 显著降低；然而，在所有受试者中，C(24) 均远高于抑制浓度 50%（IC(50) ）或抑制病毒复制一半的药物浓度。
尽管我们发现妊娠期间恩曲他滨 CL/F 升高和 C(24) 和 AUC 降低，但这些变化不足以在妊娠期间调整剂量。脐带血浓度与母体浓度相似。
