Reduced lopinavir exposure during pregnancy

Alice M. Stek, Mark Mirochnick, Edmund Capparelli, Brookie M. Best, Chengcheng Hu, Sandra K. Burchett, Carol Elgie, Diane T. Holland, Elizabeth Smith, Ruth Tuomala, Amanda Cotter, Jennifer S. Read

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

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 μg h/ml, the estimated 10th percentile LPV AUC in non-pregnant historical controls (mean AUC = 83 μg h/ml). RESULTS: Seventeen women completed antepartum evaluations; average gestational age was 35 weeks. Geometric mean antepartum LPV AUC was 44.4 μg h/ml [90% confidence interval (CI), 38.7-50.9] and 12-h post-dose concentration (C12h) was 1.6 μg/ml (90% CI, 1.1-2.5). Twelve women completed postpartum evaluations; geometric mean LPV AUC was 65.2 μg h/ml (90% CI, 49.7-85.4) and C12h was 4.6 μg/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.

Original languageEnglish (US)
Pages (from-to)1931-1939
Number of pages9
JournalAIDS
Volume20
Issue number15
DOIs
StatePublished - Oct 2006

Keywords

  • HIV
  • Lopinavir pharmacokinetics
  • Pregnancy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Stek, A. M., Mirochnick, M., Capparelli, E., Best, B. M., Hu, C., Burchett, S. K., Elgie, C., Holland, D. T., Smith, E., Tuomala, R., Cotter, A., & Read, J. S. (2006). Reduced lopinavir exposure during pregnancy. AIDS, 20(15), 1931-1939. https://doi.org/10.1097/01.aids.0000247114.43714.90