EFFECT OF GARLIC ON PHARMACOKINETICS OF SAQUINAVIR

Clinical Center

Investigators

Abstract

Complementary and alternative medicines are widely used in the HIV-infected population. Recent data have shown serious drug interactions between certain complementary medicines and protease inhibitors. Garlic is a commonly used dietary supplement, and data are available suggesting that it has single-dose inhibitory effects and multiple-dose inducing effects on cytochrome P4503A4. To evaluate the effect of garlic on the protease inhibitor saquinavir (SQV), ten healthy subjects will receive SQV (Fortovase) alone and in combination with an over-the-counter garlic preparation. SQV initially will be administered alone at a dose of 1200 mg TID for three days, and serial samples will be collected for determination of SQV pharmacokinetics after the morning dose on day 4. Beginning on day 5, garlic will be administered as one capsule TID for 21 days. On day 22 (day 18 of garlic), saquinavir will be started again at 1200 mg TID and continued for three days. On the morning of study day 25, subjects will receive their last dose of garlic and will be administered a dose of saquinavir with collection of serial samples. There will then be a 10-day washout period with no drugs, after which SQV will be given again for three days. Samples will be collected on the morning of the fourth day to evaluate the offset of the effects of garlic. SQV concentrations in plasma will be determined using a validated HPLC method. Steady-state noncompartmental parameters of SQV in the presence and absence of garlic will be determined. Pharmacokinetic parameters will be compared using an ANOVA that will include factors for a period effect and a treatment effect. Statistical analyses will include calculation of the mean ratio of the AUC in the treatment phases compared with saquinavir alone and determination of 95 percent confidence intervals. This study will help define the drug interaction potential of complementary and alternative therapies in HIV-infected patients.