Reduced lopinavir exposure during pregnancy

被引:150
作者
Stek, Alice M.
Mirochnick, Mark
Capparelli, Edmund
Best, Brookie M.
Hu, Chengcheng
Burchett, Sandra K.
Elgie, Carol
Holland, Diane T.
Smith, Elizabeth
Tuomala, Ruth
Cotter, Amanda
Read, Jennifer S.
机构
[1] Univ So Calif, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA USA
[2] Boston Univ, Boston, MA 02215 USA
[3] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA
[4] Univ Calif San Diego, Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA
[5] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA
[6] Childrens Hosp Boston, Boston, MA USA
[7] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA
[8] NIAID, Bethesda, MD 20892 USA
[9] Brigham & Womens Hosp, Boston, MA 02115 USA
[10] Univ Miami, Miami, FL 33152 USA
[11] NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, DHHS, Bethesda, MD USA
关键词
lopinavir pharmacokinetics; pregnancy; HIV;
D O I
10.1097/01.aids.0000247114.43714.90
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Optimal antiretroviral exposure during pregnancy is critical for prevention of mother-to-child HIV transmission and for maternal health. Pregnancy can alter antiretroviral pharmacokinetics. Our objective was to describe lopinavir/ritonavir (LPV/r) pharmacokinetics during pregnancy. Methods: We performed intensive steady-state 12-h pharmacokinetic profiles of lopinavir and ritonavir (three capsules: LPV 400 mg/r 100 mg) at 30-36 weeks gestation and 6-12 weeks postpartum. Maternal and umbilical cord blood samples were obtained at delivery. We measured LPV and ritonavir by reverse-phase high-performance liquid chromatography. Target LPV area under concentration versus time curve (AUC) was >= 52 mu g h/ml, the estimated 10th percentile LPV AUC in non-pregnant historical controls (mean AUC = 83 mu g h/ml). Results: Seventeen women completed antepartum evaluations; average gestational age was 35 weeks. Geometric mean antepartum LPV AUC was 44.4 mu g h/ml [90% confidence interval (CI), 38.7-50.9] and 12-h post-dose concentration (C-12h) was 1.6 mu g/ml (90% CI, 1.1-2.5). Twelve women completed postpartum evaluations; geometric mean LPV AUC was 65.2 mu g h/ml (90% CI, 49.7-85.4) and C-12h was 4.6 mu g/ml (90% CI, 3.7-5.7). The geometric mean ratio of antepartum/postpartum LPV AUC was 0.72 (90% CI, 0.54-0.96). Fourteen of 17 (82%) pregnant and three of 12 (25%) postpartum women did not meet our target LPV AUC. The ratio of cord blood/ maternal LPV concentration in ten paired detectable samples was 0.2 +/- 0.13. Conclusions: LPV/r exposure during late pregnancy was lower compared to postpartum and compared to non-pregnant historical controls. Small amounts of lopinavir cross the placenta. The pharmacokinetics, safety, and effectiveness of increased LPV/r dosing during the third trimester of pregnancy should be investigated. (c) 2006 Lippincott Williams & Wilkins.
引用
收藏
页码:1931 / 1939
页数:9
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