Mirochnick Mark, Best Brookie M, Stek Alice M, Capparelli Edmund, Hu Chengcheng, Burchett Sandra K, Holland Diane T, Smith Elizabeth, Gaddipati Sreedhar, Read Jennifer S
Department of Pediatrics, Boston University School of Medicine, and Infectious Disease Division, Children's Hospital Boston, Boston, MA 02118, USA.
J Acquir Immune Defic Syndr. 2008 Dec 15;49(5):485-91. doi: 10.1097/QAI.0b013e318186edd0.
Use of standard adult lopinavir/ritonavir (LPV/RTV) dosing (400/100 mg) during the third trimester of pregnancy results in reduced LPV exposure. The goal of this study was to determine LPV exposure during the third trimester of pregnancy and 2 weeks postpartum with a higher LPV/RTV dose.
The Pediatric AIDS Clinical Trials Group Protocol 1026s is an ongoing, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving LPV/RTV 400/100 mg twice daily during the second trimester and 533/133 mg twice daily during the third trimester through 2 weeks postpartum. Intensive steady state 12-hour pharmacokinetic profiles were performed during the third trimester and at 2 weeks postpartum and were optional during the second trimester. LPV and RTV were measured by reverse-phase high-performance liquid chromatography with a detection limit of 0.09 microg/mL.
Twenty-six HIV-infected pregnant women were studied. Median LPV area under the plasma concentration-time curve (AUCs) for the second trimester, third trimester, and postpartum were 57, 88, and 152 microg.h.mL, respectively. Median minimum LPV concentrations were 1.9, 4.1, and 8.3 microg/mL.
The higher LPV/RTV dose (533/133 mg) provided LPV exposure during the third trimester similar to the median AUC (80 microg.h.mL) in nonpregnant adults taking standard doses. However, the AUC on this increased dose at 2 weeks postpartum was considerably higher. These data suggest that the higher LPV/RTV dose should be used in third trimester pregnant women; that it should be considered in second trimester pregnant women, especially those who are protease inhibitor experienced; and that postpartum LPV/RTV dosing can be reduced to standard dosing by 2 weeks after delivery.
在妊娠晚期使用标准成人洛匹那韦/利托那韦（LPV/RTV）剂量（400/100毫克）会导致LPV暴露量减少。本研究的目的是确定在妊娠晚期和产后2周使用更高LPV/RTV剂量时的LPV暴露情况。
儿科艾滋病临床试验组方案1026s是一项正在进行的、针对感染HIV的孕妇抗逆转录病毒药代动力学的前瞻性、非盲研究，其中一个队列在妊娠中期接受每日两次400/100毫克的LPV/RTV，在妊娠晚期至产后2周接受每日两次533/133毫克的LPV/RTV。在妊娠晚期和产后2周进行了强化稳态12小时药代动力学分析，在妊娠中期为可选项目。通过反相高效液相色谱法测量LPV和RTV，检测限为0.09微克/毫升。
对26名感染HIV的孕妇进行了研究。妊娠中期、晚期和产后的血浆浓度-时间曲线下LPV的中位数面积（AUC）分别为57、88和152微克·小时/毫升。LPV的最低中位数浓度分别为1.9、4.1和8.3微克/毫升。
更高的LPV/RTV剂量（533/133毫克）在妊娠晚期提供的LPV暴露量与服用标准剂量的非妊娠成年人的中位数AUC（80微克·小时/毫升）相似。然而，产后2周时该增加剂量的AUC明显更高。这些数据表明，妊娠晚期孕妇应使用更高的LPV/RTV剂量；妊娠中期孕妇，尤其是那些有蛋白酶抑制剂使用经验的孕妇应考虑使用；产后LPV/RTV剂量在分娩后2周可减至标准剂量。
