title: Sex differences in lopinavir and ritonavir pharmacokinetics among HIV-infected women and men.
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.
authors.affiliation: David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Obi C
authors.initials: OC
authors.lastname: Umeh
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
authors.forename: Jeong-Gun
authors.initials: JG
authors.lastname: Park
authors.forename: Yoninah
authors.initials: Y
authors.lastname: Cramer
authors.forename: Ashwaq E
authors.initials: AE
authors.lastname: Hermes
authors.forename: Courtney V
authors.initials: CV
authors.lastname: Fletcher
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002214:Capsules; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012737:Sex Factors; D013607:Tablets; D055815:Young Adult
chemical_list: D002214:Capsules; D017320:HIV Protease Inhibitors; D013607:Tablets; D061466:Lopinavir; D019438:Ritonavir