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 RESEARCH ARTICLE
Year : 2009  |  Volume : 41  |  Issue : 4  |  Page : 167-172

Reduced exposure of imatinib after coadministration with acetaminophen in mice


1 Department of Pathology, International Medical University; No. 126, Jalan 19/155B, Bukit Jalil-57000 Kuala Lumpur, Malaysia
2 Department of Human Biology, International Medical University; No. 126, Jalan 19/155B, Bukit Jalil-57000 Kuala Lumpur, Malaysia
3 Department of Pharmaceutical Technology, International Medical University; No. 126, Jalan 19/155B, Bukit Jalil-57000 Kuala Lumpur, Malaysia

Correspondence Address:
Ignacio Segarra
Department of Pharmaceutical Technology, International Medical University; No. 126, Jalan 19/155B, Bukit Jalil-57000 Kuala Lumpur
Malaysia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.56071

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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.






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