743   Garlic Supplements Decrease Saquinavir Plasma Concentrations.

S. C. Piscitelli*¹, A. H. Burstein¹, N. Welden², K. Gallicano³, and J. Falloon².
¹Clin. Ctr. and NIAID;²NIH, Bethesda, MD; and³Axelson Biopharma Res.Vancouver, BC, Canada.

Background:Herbal therapies are widely used in HIV-infected patients despite limited data on drug interactions. Garlic supplements are commonly used to lower cholesterol in patients receiving protease inhibitors.

Methods:We evaluated the effect of garlic capsules on saquinavir pharmacokinetics in 10 healthy volunteers. Subjects received saquinavir 1200 mg TID with meals for 3 days, then had samples drawn after the morning dose on day 4. Garlic capsules (allicin content confirmed) were administered twice daily on days 5 through 24. Saquinavir was administered on days 22 through 24 and blood samples were drawn with concomitant dosing of both drugs on day 25. After a 10-day washout, saquinavir was again given for 3 days and samples were collected on the 4th day of dosing. Saquinavir concentrations were determined by a LC/MS method, and statistical tests were based on geometric means.

Results:Nine subjects were included in the analysis; one subject was excluded due to nonadherence with study procedures. In the presence of garlic supplementation, mean saquinavir AUC decreased 51% from 3382 to 1673 ng*h/ml (range -84% to +12%, p = 0.007). Mean trough levels at 8 hours postdose decreased 49% from 108 to 55 ng/ml (range -82% to +33%, p = 0.002), and mean C_maxdecreased 54% from 1190 to 543 ng/ml (range -88% to +30%, p = 0.006). After the 10-day washout, AUC, trough, and C_maxvalues returned to only 60—70% of baseline values.

Conclusions:Chronic dosing of garlic supplements significantly decreased plasma concentrations of saquinavir. Patients should use caution when combining garlic supplements with saquinavir used as a sole protease inhibitor.