Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis

Eur J Clin Pharmacol. 2005 Mar;61(1):1-7. doi: 10.1007/s00228-004-0843-z. Epub 2005 Jan 22.

Abstract

Objectives: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Drug Interactions
  • HIV Protease Inhibitors / blood
  • HIV Protease Inhibitors / pharmacokinetics*
  • Half-Life
  • Humans
  • Indinavir / blood
  • Indinavir / pharmacokinetics*
  • Male
  • Meta-Analysis as Topic
  • Milk Thistle*
  • Plant Preparations / pharmacology*

Substances

  • HIV Protease Inhibitors
  • Plant Preparations
  • Indinavir