TY - JOUR
T1 - Milk thistle and indinavir
T2 - A randomized controlled pharmacokinetics study and meta-analysis
AU - Mills, Edward
AU - Wilson, Kumanan
AU - Clarke, Mike
AU - Foster, Brian
AU - Walker, Scott
AU - Rachlis, Beth
AU - DeGroot, Nick
AU - Montori, Victor M.
AU - Gold, Wayne
AU - Phillips, Elizabeth
AU - Myers, Stephen
AU - Gallicano, Keith
N1 - Funding Information:
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.
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
KW - Drug interactions
KW - Indinavir
KW - Milk thistle
KW - Pharmacokinetics
KW - Randomized controlled trial
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U2 - 10.1007/s00228-004-0843-z
DO - 10.1007/s00228-004-0843-z
M3 - Article
C2 - 15666173
AN - SCOPUS:20244375242
SN - 0031-6970
VL - 61
SP - 1
EP - 7
JO - European Journal of Clinical Pharmacology
JF - European Journal of Clinical Pharmacology
IS - 1
ER -