| RESEARCH ARTICLE |
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| Year : 2009 | Volume
: 41
| Issue : 4 | Page : 167-172 |
Reduced exposure of imatinib after coadministration with acetaminophen in mice
Inthisham Nassar1, Thanikachalam Pasupati1, John Paul Judson2, Ignacio Segarra3
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
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0253-7613.56071
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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