Sex differences in lopinavir and ritonavir pharmacokinetics among HIV-infected women and men

Obi C. Umeh, Judith S. Currier, Jeong Gun Park, Yoninah Cramer, Ashwaq E. Hermes, Courtney V. Fletcher

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The authors compared the pharmacokinetics of lopinavir (LPV) and ritonavir (RTV) between women and men. This 2-step, multicenter, pharmacokinetic study enrolled human immunodeficiency virus (HIV)-infected adults on lopinavir/ritonavir (LPV/r) capsules (400/100 mg bid) plus 1 or more nucleoside reverse transcriptase inhibitors. All participants underwent 12-hour pharmacokinetic sampling. The pharmacokinetic sampling was repeated in participants receiving the LPV/r tablet formulation. Step 1 enrolled 37 women and 40 men; step 2 included 42 participants from step 1 plus 35 new participants (39 women and 38 men). LPV pharmacokinetics in women and men were not significantly different with either formulation. Women had significantly higher median RTV AUC0-12 h with both the soft-gel capsule (SGC) and tablet formulations (SGC: 5395 vs 4119 ng•h/mL, P =.026; tablet: 5310 vs 3941 ng•h/mL, P =.012), higher median Cmax (SGC: 802 vs 635 ng/mL, P =.032; tablet: 773 vs 570 ng/mL, P =.006), and lower median CL/F (SGC: 18.54 vs 24.31 L/h, P =.026; tablet: 18.83 vs 25.37 L/h, P =.012). RTV CL/F was slower in women after weight adjustment with both formulations. The pharmacokinetics of LPV in the SGC and tablet formulations are comparable in HIV-infected patients. Women had higher RTV AUC0-12 h and lower CL/F with both formulations. The mechanism of the sex difference in RTV CL/F warrants elucidation.

Original languageEnglish (US)
Pages (from-to)1665-1673
Number of pages9
JournalJournal of Clinical Pharmacology
Volume51
Issue number12
DOIs
StatePublished - Dec 1 2011

Keywords

  • HIV infection
  • lopinavir/ritonavir
  • pharmacokinetics
  • sex differences

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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