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, 41 (4), 167-72

Reduced Exposure of Imatinib After Coadministration With Acetaminophen in Mice

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Reduced Exposure of Imatinib After Coadministration With Acetaminophen in Mice

Inthisham Nassar et al. Indian J Pharmacol.

Abstract

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.

Figures

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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References

    1. Scripture CD, Figg WD. Drug interactions in cancer therapy. Nat Rev Cancer. 2006;6:546–58. - PubMed
    1. Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood. 2005;105:2640–53. - PubMed
    1. Dagher R, Cohen M, Williams G, Rothmann M, Gobburu J, Robbie G, et al. Approval summary: Imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clin Cancer Res. 2002;8:3034–8. - PubMed
    1. Bolton A, Peng B, Hubert M, Krebs-Brown A, Keller U, Seiberling MI. Effect of rifampicin on the pharmacokinetics of imatinib mesylate (Gleevec, STI571) in healthy subjects. Cancer Chemother Pharmacol. 2004;53:102–6. - PubMed
    1. Kajita T, Higashi Y, Imamura M, Maida C, Fujii Y, Yamamoto I, et al. Effect of imatinib mesylate on the disposition kinetics of cyclosporine in rats. J Pharm Pharmacol. 2006;58:997–1000. - PubMed

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