title: Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis.
abstract: 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.
authors.affiliation: Faculty of Health Sciences, Clinical Epidemiology and Biostatistics, McMaster University, HSC-2C12, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada. millsej@mcmaster.ca
authors.forename: Edward
authors.initials: E
authors.lastname: Mills
authors.forename: Kumanan
authors.initials: K
authors.lastname: Wilson
authors.forename: Mike
authors.initials: M
authors.lastname: Clarke
authors.forename: Brian
authors.initials: B
authors.lastname: Foster
authors.forename: Scott
authors.initials: S
authors.lastname: Walker
authors.forename: Beth
authors.initials: B
authors.lastname: Rachlis
authors.forename: Nick
authors.initials: N
authors.lastname: DeGroot
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
authors.forename: Wayne
authors.initials: W
authors.lastname: Gold
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Phillips
authors.forename: Stephen
authors.initials: S
authors.lastname: Myers
authors.forename: Keith
authors.initials: K
authors.lastname: Gallicano
mesh_terms: 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*
chemical_list: D017320:HIV Protease Inhibitors; D028321:Plant Preparations; D019469:Indinavir