Lopinavir/Ritonavir pharmacokinetic profile: impact of sex and other covariates following a change from twice-daily to once-daily therapy.
The aim of this study was to determine the impact of sex on the pharmacokinetics of lopinavir/ritonavir. Interaction between lopinavir/ritonavir and tenofovir was also evaluated. Steady-state plasma samples were obtained from virologically suppressed HIV-infected patients on lopinavir/ritonavir 800/200-mg soft gel capsule taken once daily. Drug assays were performed by high-performance liquid chromatography. Pharmacokinetic parameters estimated by noncompartmental method were reported as 90% confidence intervals (CIs) about the geometric mean ratio (GMR). There were 9 males and 11 females. No sex differences were observed in lopinavir/ritonavir pharmacokinetics profile. The GMR(sex) (women compared with men) for lopinavir area under the concentration-time curve (AUC(24)), maximum concentration (C(max)), and minimum concentration (C(min)) was 0.95 (90% CI, 0.70-1.29), 0.88 (90% CI, 0.67-1.15), and 1.27 (90% CI, 0.60-2.66), respectively. Similarly, the GMR(sex) for ritonavir AUC(24), C(max), and C(min) was 0.84 (90% CI, 0.57-1.24), 0.79 (90% CI, 0.50-1.22), and 1.02 (90% CI, 0.58-1.80), respectively. Tenofovir coadministration led to a reduction in lopinavir/ritonavir plasma exposure, giving a lopinavir GMR(tenofovir) for C(max) of 0.72 (90% CI, 0.57-0.93) and AUC(24) of 0.74 (90% CI, 0.56-0.98), respectively. No difference in lopinavir/ritonavir plasma concentrations between sexes was demonstrated in this study. However, tenofovir coadministration lowered lopinavir/ritonavir plasma exposure.
Ofotokun
Ighovwerha
I
Department of Medicine, Division of Infectious Diseases, Emory University of Medicine, 69 Jesse Hill Jr Drive Atlanta, GA 30303, USA.
Chuck
Susan K
SK
Binongo
Jose N
JN
Palau
Mauricio
M
Lennox
Jeffrey L
JL
Acosta
Edward P
EP
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D019540:Area Under Curve; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D061466:Lopinavir; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012737:Sex Factors; D000068698:Tenofovir
D002214:Capsules; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir