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

TitleSex differences in lopinavir and ritonavir pharmacokinetics among HIV-infected women and men.
Publication TypeJournal Article
Year of Publication2011
AuthorsUmeh OC, Currier JS, Park J-G, Cramer Y, Hermes AE, Fletcher CV
JournalJ Clin Pharmacol
Volume51
Issue12
Pagination1665-73
Date Published2011 Dec
ISSN1552-4604
KeywordsAdolescent, Adult, Area Under Curve, Capsules, Female, HIV Infections, HIV Protease Inhibitors, Humans, Lopinavir, Male, Middle Aged, Ritonavir, Sex Factors, Tablets, Young Adult
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 AUC(0-12 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 C(max) (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 AUC(0-12 h) and lower CL/F with both formulations. The mechanism of the sex difference in RTV CL/F warrants elucidation.

DOI10.1177/0091270010388650
Alternate JournalJ Clin Pharmacol
PubMed ID21233301
PubMed Central IDPMC3325020
Grant ListAI-38858 / AI / NIAID NIH HHS / United States
AI-68634 / AI / NIAID NIH HHS / United States
K24 AI 56933 / AI / NIAID NIH HHS / United States
K24 AI056933 / AI / NIAID NIH HHS / United States
UL1 RR025014 / RR / NCRR NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069424-07 / AI / NIAID NIH HHS / United States
UOI AI 069424 / AI / NIAID NIH HHS / United States
UOI AI68636 / AI / NIAID NIH HHS / United States