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Published on: December 7, 2014
Does Crizotinib Auto-Inhibit CYP3A in vivo?
Abigail R Bland1, Nensi Shrestha1, Rhonda J Rosengren1
1Department of Pharmacology & Toxicology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
Abstract:
Crizotinib is a tyrosine kinase inhibitor used to treat anaplastic lymphoma kinase-positive lung cancer. There is in vitro evidence that crizotinib may auto-inhibit cytochrome P450 3A (CYP3A) activity, with important implications for crizotinib pharmacokinetics. In order to test whether crizotinib treatment alters CYP3A activity in vivo, mice were treated with 5 and 25 mg/kg crizotinib (p.o.) daily for 14 days. Results showed that crizotinib treatment did not alter CYP3A activity as determined by erythromycin N-demethylation. In addition, CYP3A polypeptide expression as measured by Western blot was unchanged. Therefore, our results do not support CYP3A inhibition by crizotinib in vivo.
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