Title | Sex differences in lopinavir and ritonavir pharmacokinetics among HIV-infected women and men. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Umeh OC, Currier JS, Park J-G, Cramer Y, Hermes AE, Fletcher CV |
Journal | J Clin Pharmacol |
Volume | 51 |
Issue | 12 |
Pagination | 1665-73 |
Date Published | 2011 Dec |
ISSN | 1552-4604 |
Keywords | Adolescent, 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. |
DOI | 10.1177/0091270010388650 |
Alternate Journal | J Clin Pharmacol |
PubMed ID | 21233301 |
PubMed Central ID | PMC3325020 |
Grant List | AI-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 |