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Effect of St. John's Wort on imatinib mesylate pharmacokinetics
Author(s) -
Frye R. F.,
Fitzgerald S. M.,
Lagattuta T. F.,
Egorin M. J.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.367
Subject(s) - imatinib mesylate , pharmacokinetics , pharmacology , mesylate , imatinib , medicine , chemistry , organic chemistry , myeloid leukemia
Purpose Imatinib, a potent Bcr‐Abl tyrosine kinase inhibitor, is very active against Philadelphia chromosome‐positive chronic myelogenous leukemia. Since imatinib is predominately metabolized by CYP3A4, its pharmacokinetics may be altered when it is co‐administered with drugs/herbs (e.g., St. John's Wort (SJW)) that modulate CYP3A4 activity. Thus, we examined the effects of SJW on imatinib pharmacokinetics. Methods. Twelve healthy subjects (6 men/6 women) between the ages of 20 and 51 yrs participated. Each subject received imatinib 400 mg orally on day 1, SJW (300 mg TID) on days 3–17, and imatinib 400 mg again on day 15. Serial blood samples were obtained over 72 hours after each imatinib dose. Imatinib and its metabolite CGP 74588 were quantified by LC‐MS. Results. SJW increased imatinib clearance by 44% (p<0.001) from 12.5 L/hr to 17.9 L/hr; AUC was decreased by 30% from 34.5 μg×hr/ml to 24.2 μg×hr/ml. Half‐life (12.8 hrs vs. 9.0 hrs) and Cmax (2.2 μg/ml vs. 1.8 μg/ml) were also significantly decreased (p<0.005). Conclusions. These data indicate that SJW increases imatinib clearance. Thus, patients on imatinib should avoid taking SJW. Concomitant SJW use may necessitate an increase in the imatinib dose to maintain clinical effectiveness. Clinical Pharmacology & Therapeutics (2004) 75 , P96–P96; doi: 10.1016/j.clpt.2003.11.367