Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis.
OBJECTIVE
To determine whether ingestion of milk thistle affects the pharmacokinetics of indinavir.


METHODS
We conducted a three-period, randomized controlled trial with 16 healthy participants. We randomized participants to milk thistle or control. All participants received initial dosing of indinavir, and baseline indinavir levels were obtained (AUC(0-8)) (phase I). The active group were then given 450 mg milk-thistle extract capsules to be taken t.i.d. from day 2 to day 30. The control group received no plant extract. On day 29 and day 30, indinavir dosing and sampling was repeated in both groups as before (phase II). After a wash-out period of 7 days, indinavir dosing and sampling were repeated as before (phase III).


RESULTS
All participants completed the trial, but two were excluded from analysis due to protocol violation. There were no significant between-group differences. Active group mean AUC(0-8) indinavir decreased by 4.4% (90% CI, -27.5% to -26%, P=0.78) from phase I to phase II in the active group, and by 17.3% (90% CI, -37.3% to +9%, P=0.25) in phase III. Control group mean AUC(0-8) decreased by 21.5% (90% CI, -43% to +8%, P=0.2) from phase I to phase II and by 38.5% (90% CI, -55.3% to -15.3%, P=0.01) of baseline at phase III. To place our findings in context, milk thistle-indinavir trials were identified through systematic searches of the literature. A meta-analysis of three milk thistle-indinavir trials revealed a non-significant pooled mean difference of 1% in AUC(0-8) (95% CI, -53% to 55%, P=0.97).


CONCLUSIONS
Indinavir levels were not reduced significantly in the presence of milk thistle.
Mills
Edward
E
Faculty of Health Sciences, Clinical Epidemiology and Biostatistics, McMaster University, HSC-2C12, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada. millsej@mcmaster.ca
Wilson
Kumanan
K
Clarke
Mike
M
Foster
Brian
B
Walker
Scott
S
Rachlis
Beth
B
DeGroot
Nick
N
Montori
Victor M
VM
Gold
Wayne
W
Phillips
Elizabeth
E
Myers
Stephen
S
Gallicano
Keith
K
D000328:Adult; D019540:Area Under Curve; D004347:Drug Interactions; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D019469:Indinavir / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D015201:Meta-Analysis as Topic; D020944:Silybum marianum; D028321:Plant Preparations / Q000494:pharmacology*
D017320:HIV Protease Inhibitors; D028321:Plant Preparations; D019469:Indinavir