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.
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Acknowledgements
This study was supported by The Ontario HIV Treatment Network. Edward Mills conceptualized the study, obtained funding, conducted the trial and wrote the manuscript. Kumanan Wilson co- conceptualized the study, obtained funding, conducted the trial and wrote the manuscript. Mike Clarke assisted in trial design, provided critical insights in conduct and co-wrote the manuscript. Brian Foster assisted in obtaining funding, analysis of the plant extract and co-wrote the manuscript. Scott Walker assisted in obtaining funding, analysis of blood and co-wrote the manuscript. Beth Rachlis enrolled participants and coordinated the study. Nick DeGroot assisted in trial planning, coordination and co-wrote the manuscript. Victor Montori conducted the meta-analysis. Wayne Gold assisted in trial monitoring and conducted all patient-related management. Elizabeth Phillips assisted in obtaining funding, design of trial, interpretation of results and co-wrote the manuscript. Stephen Myers assisted in patient management and trial planning. He co-wrote the manuscript. Keith Gallicano assisted in obtaining funding, trial design, analysis of blood and statistics. He co-wrote the manuscript. The authors have no conflicts of interest.
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Mills, E., Wilson, K., Clarke, M. et al. Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis. Eur J Clin Pharmacol 61, 1–7 (2005). https://doi.org/10.1007/s00228-004-0843-z
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DOI: https://doi.org/10.1007/s00228-004-0843-z