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Effect of Milk Thistle on the Pharmacokinetics of Indinavir in Healthy Volunteers
Author(s) -
Piscitelli Stephen C.,
Formentini Elizabeth,
Burstein Aaron H.,
Alfaro Raul,
Jagannatha Shyla,
Falloon Judith
Publication year - 2002
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.22.8.551.33205
Subject(s) - indinavir , pharmacokinetics , dosing , milk thistle , cmax , medicine , pharmacology , cmin , area under the curve , human immunodeficiency virus (hiv) , sida , immunology , viral disease
Study Objective. To characterize the pharmacokinetics of indinavir in the presence and absence of milk thistle and to determine the offset of any effect of milk thistle on indinavir disposition. Design. Prospective open‐label drug interaction study. Setting. Outpatient clinic. Subjects. Ten healthy volunteers. Intervention. Blood samples were collected over 8 hours after the volunteers took four doses of indinavir 800 mg every 8 hours on an empty stomach for baseline pharmacokinetics. This dosing and sampling were repeated after the subjects took milk thistle 175 mg (confirmed to contain silymarin 153 mg, the active ingredient) 3 times/day for 3 weeks. After an 11‐day washout, indinavir dosing and blood sampling were repeated to evaluate the offset of any potential interaction. Measurements and Main Results. Indinavir concentrations were measured by using a validated high‐performance liquid chromatography method. The following pharmacokinetic parameters were determined: highest concentration (C max ), hour‐0 concentration, hour‐8 concentration (C 8 ), time to reach C max , and area under the plasma concentration‐time curve over the 8‐hour dosing interval (AUC 8 ). Milk thistle did not alter significantly the overall exposure of indinavir, as evidenced by a 9% reduction in the indinavir AUC 8 after 3 weeks of dosing with milk thistle, although the least squares mean trough level (C 8 ) was significantly decreased by 25%. Conclusion. Milk thistle in commonly administered dosages should not interfere with indinavir therapy in patients infected with the human immunodeficiency virus.