Coadministration of milk thistle and indinavir in healthy subjects

Study Objective. To determine if milk thistle (silymarin) alters the pharmacokinetics of indinavir. Design. Sequential crossover trial. Setting. General clinical research center. Subjects. Ten healthy subjects. Intervention. Indinavir 800 mg 3 times/day was given for four doses on days 1 and 2. Silymarin 160 mg 3 times/day was given on days 3–15. On day 16 and for one dose on day 17, both drugs were given at the same dosages. Measurements and Main Results. Indinavir's pharmacokinetic parameters were evaluated at steady state both before and after administration of 14 days of silymarin. Blood samples were collected −0.25, 0.5, 1, 2, 3, 4, and 5 hours after indinavir dosing and assayed by high-performance liquid chromatography. The final pharmacokinetic model had first-order absorption after a lag time, and two compartments with first-order elimination from the central compartment. When given alone and combined with silymarin, respectively, the geometric mean (95% confidence interval [CI]) steady-state indinavir area under the plasma concentration-time curve was 20.7 hr·mg/L (15.3–28.2 hr·mg/L) and 19.4 hr·mg/L (15.8–23.6 hr·mg/L) and the trough plasma concentration was 0.340 mg/L (0.232–0.497 mg/L) and 0.232 mg/L (0.129–0.419 mg/L). Conclusion. Silymarin has no apparent effect on indinavir plasma concentrations.