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 (AUC0-24) in the female patients (82,300 ng x hr/ml) was significantly (p=0.036) higher than that in the male patients (47,400 ng x hr/ml). This relationship remained significant for weight-adjusted saquinavir AUC0-24 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.