Sex-related differences in the pharmacokinetics of once-daily saquinavir soft-gelatin capsules boosted with low-dose ritonavir in patients infected with human immunodeficiency virus type 1

Study Objectives. To compare the steady-state pharmacokinetics and safety of saquinavir soft-gelatin capsules (SGC) plus low-dose ritonavir administered once/day in antiretroviral-naive adult patients infected with the human immunodeficiency virus type 1 (HIV-1) and to evaluate any sex-related differences. Design. Single-center, open-label, pharmacokinetic study Setting. University-affiliated outpatient HIV clinic. Patients. Six men and seven women with HIV-1, Intervention. Each patient received saquinavir SGC 1600 mg and ritonavir 100 mg for a 14-day course of therapy Nine serial blood samples during 24 hours were collected on day 14 of therapy. Measurements and Main Results. Plasma saquinavir and ritonavir concentrations were measured by high-performance liquid chromatography Standard noncompartmental methods were used to calculate the pharmacokinetic parameters. The unpaired Student t test was used for the statistical comparison of pharmacokinetic parameters between male and female patients. Once-daily saquinavir SGC plus ritonavir was generally well tolerated. Pharmacokinetic data from five men and five women were evaluable. The median saquinavir area under the concentration-time curve from 0-24 hours (AUC(0-24)) in the female patients (82,300 ng(.)hr/ml) was significantly (p=0.036) higher than that in the male patients (47,400 ng(.)hr/ml). This relationship remained significant for weight-adjusted saquinavir AUC(0-24) values. Ritonavir's apparent oral clearance in the women was significantly (p=0.023) lower than that in the men. Conclusion. Significantly higher plasma concentrations of saquinavir were achieved in female compared with male HIV-infected patients receiving once-daily saquinavir SGC 1600 mg plus ritonavir 100 mg.