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Updated: Jun 12, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Reduced exposure of imatinib after coadministration with acetaminophen in mice
Inthisham Nassar1, Thanikachalam Pasupati, John Paul Judson
1Departments of Pathology, International Medical University; No. 126, Jalan 19/155B, Bukit Jalil-57000 Kuala Lumpur, Malaysia.
Purpose:
Imatinib is an efficacious drug against chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST) due to selective inhibition of c-KIT and BCR-ABL kinases. It presents almost complete bioavailability, is eliminated via P450-mediated metabolism and is well tolerated. However, a few severe drug-drug interactions have been reported in cancer patients taking acetaminophen.
Materials And Methods:
Male ICR mice were given 100 mg/kg single dose of imatinib orally or imatinib 100 mg/kg (orally) coadministered with acetaminophen intraperitoneally (700 mg/kg). Mice were euthanized at predetermined time points, blood samples collected, and imatinib plasma concentration measured by HPLC.
Results:
Imatinib AUC(0-12) was 27.04 +/- 0.38 mg.h/ml, C(max) was 7.21 +/- 0.99 mg/ml and elimination half-life was 2.3 hours. Acetaminophen affected the imatinib disposition profile: AUC(0-12) and C(max) decreased 56% and 59%, respectively and a longer half-life was observed (5.6 hours).
Conclusions:
The study shows a pharmacokinetic interaction between acetaminophen and imatinib which may render further human studies necessary if both drugs are administered concurrently to cancer patients.
