The influence of St. John's wort on the pharmacokinetics and protein binding of imatinib mesylate.
OBJECTIVE
To determine the effect of St. John's wort on the pharmacokinetics of imatinib mesylate.


METHODS
Open-label, complete crossover, fixed-sequence, pharmacokinetic study.


METHODS
Clinical research center.


METHODS
Ten healthy adult volunteers.


METHODS
Single 400-mg oral doses of imatinib were administered before and after 2 weeks of treatment with St. John's wort 300 mg 3 times/day.


RESULTS
The pharmacokinetics of imatinib were significantly altered by St. John's wort, with reductions of 32% in the median area under the concentration-time curve from time zero to infinity (p=0.0001), 29% in maximum observed concentration (p=0.005), and 21% in half-life (p=0.0001). Protein binding ranged from 97.7-90.3% (mean 94.9%), was concentration independent, and was not altered by St. John's wort. Therapeutic outcomes of imatinib have been shown to correlate with both dose and drug concentrations.


CONCLUSIONS
Coadministration of imatinib with St. John's wort may compromise imatinib's clinical efficacy.
Smith
Patrick
P
School of Pharmacy and Pharmaceutical Sciences, University of Buffalo, Buffalo, New York, USA.
Bullock
Julie M
JM
Booker
Brent M
BM
Haas
Curtis E
CE
Berenson
Charles S
CS
Jusko
William J
WJ
D000284:Administration, Oral; D000328:Adult; D000970:Antineoplastic Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001549:Benzamides; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D020902:Hypericum; D000068877:Imatinib Mesylate; D008297:Male; D008657:Metabolic Clearance Rate; D010879:Piperazines / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D028321:Plant Preparations / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011743:Pyrimidines / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D028321:Plant Preparations; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A