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, 41 (4), 167-72

Reduced Exposure of Imatinib After Coadministration With Acetaminophen in Mice


Reduced Exposure of Imatinib After Coadministration With Acetaminophen in Mice

Inthisham Nassar et al. Indian J Pharmacol.


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.

Keywords: Acetaminophen; chronic myeloid leukemia; drug–drug interaction; gastrointestinal stromal tumor; imatinib; pharmacokinetics.


Figure 1
Figure 1
HPLC analysis of imatinib: (a) Chromatogram showing the absence of interference between acetaminophen and imatinib; (b) Chromatogram of a blank plasma sample showing the lack of matrix interference; (c) Chromatogram of a plasma sample at 40 min after coadministration of acetaminophen (700 mg/kg, IP) and imatinib (100 mg/kg, PO). The additional peaks at 3.6 and 5.5 min are likely to be imatinib metabolites.
Figure 2
Figure 2
Plasma concentration-time curve profile of imatinib after oral administration to mice

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