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.
OBJECTIVE
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.


METHODS
Single-center, open-label, pharmacokinetic study.


METHODS
University-affiliated outpatient HIV clinic.


METHODS
Six men and seven women with HIV-1.


METHODS
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


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.


CONCLUSIONS
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.
Pai
Manjunath P
MP
University of New Mexico Health Sciences Center, Albuquerque, USA.
Schriever
Christopher A
CA
Diaz-Linares
Mariela
M
Novak
Richard M
RM
Rodvold
Keith A
KA
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015497:HIV-1; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000627:therapeutic use; D019258:Saquinavir / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012727:Sex Characteristics
D002214:Capsules; D017320:HIV Protease Inhibitors; D019258:Saquinavir; D019438:Ritonavir