Lopinavir exposure with an increased dose during pregnancy

Mark Mirochnick, Brookie M. Best, Alice M. Stek, Edmund Capparelli, Chengcheng Hu, Sandra K. Burchett, Diane T. Holland, Elizabeth Smith, Sreedhar Gaddipati, Jennifer S. Read

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Background: 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. Methods: 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 highperformance liquid chromatography with a detection limit of 0.09 μg/mL. Results: 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 μg-h -1-mL -1, respectively. Median minimum LPV concentrations were 1.9, 4.1, and 8.3 μg/mL. Conclusions: The higher LPV/RTV dose (533/133 mg) provided LPV exposure during the third trimester similar to the median AUC (80 μg-h -1-mL -1) 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.

Original languageEnglish (US)
Pages (from-to)485-491
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume49
Issue number5
DOIs
StatePublished - Dec 2008

Keywords

  • HIV lopinavir
  • Mother-to-child transmission
  • Pharmacokinetics
  • Pregnancy

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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