Coadministration of milk thistle and indinavir in healthy subjects.
OBJECTIVE
To determine if milk thistle (silymarin) alters the pharmacokinetics of indinavir.


METHODS
Sequential crossover trial.


METHODS
General clinical research center.


METHODS
Ten healthy subjects.


METHODS
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.


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 x mg/L (15.3-28.2 hr x mg/L) and 19.4 hr x mg/L (15.8-23.6 hr x 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).


CONCLUSIONS
Silymarin has no apparent effect on indinavir plasma concentrations.
DiCenzo
Robert
R
University of Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, New York, USA.
Shelton
Mark
M
Jordan
Kelly
K
Koval
Christine
C
Forrest
Alan
A
Reichman
Richard
R
Morse
Gene
G
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D019469:Indinavir / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D020944:Silybum marianum / Q000737:chemistry; D020011:Protective Agents / Q000494:pharmacology*; D012838:Silymarin / Q000494:pharmacology*
D017320:HIV Protease Inhibitors; D020011:Protective Agents; D012838:Silymarin; D019469:Indinavir