European Journal of Clinical Pharmacology

, Volume 61, Issue 1, pp 1–7

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
Clinical Trials

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 (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.

Keywords

Milk thistle Indinavir Randomized controlled trial Pharmacokinetics Drug interactions 

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Edward Mills
    • 1
  • Kumanan Wilson
    • 2
  • Mike Clarke
    • 3
  • Brian Foster
    • 4
  • Scott Walker
    • 5
  • Beth Rachlis
    • 6
  • Nick DeGroot
    • 6
  • Victor M. Montori
    • 7
  • Wayne Gold
    • 2
  • Elizabeth Phillips
    • 2
    • 5
  • Stephen Myers
    • 8
  • Keith Gallicano
    • 9
  1. 1.Faculty of Health Sciences, Clinical Epidemiology and BiostatisticsMcMaster UniversityHamiltonCanada
  2. 2.Department of MedicineUniversity of TorontoCanada
  3. 3.UK Cochrane CentreOxfordUK
  4. 4.Therapeutic Products DirectorateHealth CanadaCanada
  5. 5.Sunnybrooke and Women’s College HospitalTorontoCanada
  6. 6.Canadian College of Naturopathic MedicineCanada
  7. 7.Department of MedicineMayo ClinicRochesterUSA
  8. 8.Department of MedicineUniversity of QueenslandBrisbaneAustralia
  9. 9.Watson LaboratoriesCoronaUSA

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