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

Edward Mills, Kumanan Wilson, Mike Clarke, Brian Foster, Scott Walker, Beth Rachlis, Nick DeGroot, Victor M. Montori, Wayne Gold, Elizabeth Phillips, Stephen Myers, Keith Gallicano

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59 Scopus citations


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 (AUC0-8) (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 AUC0-8 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 AUC0-8 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 AUC0-8 (95% CI, -53% to 55%, P=0.97). Conclusions: Indinavir levels were not reduced significantly in the presence of milk thistle.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalEuropean Journal of Clinical Pharmacology
Issue number1
StatePublished - Mar 1 2005



  • Drug interactions
  • Indinavir
  • Milk thistle
  • Pharmacokinetics
  • Randomized controlled trial

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Mills, E., Wilson, K., Clarke, M., Foster, B., Walker, S., Rachlis, B., DeGroot, N., Montori, V. M., Gold, W., Phillips, E., Myers, S., & Gallicano, K. (2005). Milk thistle and indinavir: A randomized controlled pharmacokinetics study and meta-analysis. European Journal of Clinical Pharmacology, 61(1), 1-7.