Effect of St John's wort on imatinib mesylate pharmacokinetics

Abstract

These data indicate that St John's wort increases imatinib clearance. Thus patients taking imatinib should avoid taking St John's wort. Concomitant use of enzyme inducers, including St John's wort, may necessitate an increase in the imatinib dose to maintain clinical effectiveness.

CYP3A activity influences imatinib response in patients with chronic myeloid leukemia: a pilot study on in vivo CYP3A activity

“…However, it is not known whether intra-individual CYP3A4 activity is changed upon long-term imatinib therapy, although it has been shown that CYP3A4 inducers and inhibitors may alter the pharmacokinetics of imatinib [14][15][16]. The MTT data demonstrate potencies in the same range for imatinib (IC 50 = 0.32 µM, n=3, CV = 12%) and its main metabolite (IC 50 = 0.91 µM, n=3, CV = 15%), as demonstrated by others [2].…”

Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia

“…Drugs that inhibit or induce CYP3A4 can also alter imatinib PKs. Inhibitors of CYP3A4, such as ketaconazole 22 may increase imatinib concentrations; conversely, inducers of CYP3A4, such as rifampicin, 21 some antiepileptic drugs 56 and the herbal remedy St John's wort, 30,31 may decrease imatinib concentrations. Patients should thus be asked about their use of over-thecounter as well as prescription medications.…”

“…18 Some herbal medicines (for example, St John's wort) and consumer products (for example, grapefruit juice) can also affect CYP3A4 activity and hence imatinib PK. 30,31 Physicians should be aware of these possibilities when treating patients with imatinib. Studies investigating the significance of polymorphisms of cytochrome P450 enzymes in determining plasma concentrations and response to therapy are needed to understand the significance of these factors better.…”

Dietary Supplement Use in Cancer Care: Help or Harm

“…Ten subjects, given 400 mg of imatinib before and after a treatment with 300 mg of St. John's wort three times a day [47] showed significant alterations in the pharmacokinetics of imatinib (32% reduction in AUC and a 29% reduction in maximal concentration). In a second study, 12 healthy subjects who were given 300 mg of a standardized proprietary St. John's wort product three times a day also had a significant increase in imatinib clearance (43%), as well as a 30% reduction in AUC [48]. Significant reductions were also noted in half-life and maximum concentrations.…”