期刊
CLINICAL THERAPEUTICS
卷 38, 期 1, 页码 216-220出版社
ELSEVIER
DOI: 10.1016/j.clinthera.2015.10.017
关键词
adverse drug event; CEP72; CYP; vincristine; neuropathy; P-glycoprotein; pharmacogenetics; phenotyping
Purpose: Peripheral neuropathy is a frequent vincristine-induced adverse effect. Vincristine is a substrate of P-glycoprotein and is metabolized by the cytochrome P-450 (CYP) 3A5 and 3A4 isoforms, with CYP3A5 contributing to 75% of the intrinsic clearance of vincristine. Alterations in the function of these proteins may lead to an increase in vincristine toxicity. CYP3A5 nonexpressor status has been associated with vincristine-induced peripheral neuropathy. The severity of neuropathy has been reported to be inversely correlated to vincristine metabolite concentrations. Recently, the presence of a mutation in the CEP72 gene, which encodes for a protein involved in microtubule formation, has also been associated with vincristine-induced peripheral neuropathy. However, a clear correlation between genetic polymorphisms and vincristine toxicity has not been established. Methods: Here we report the case of a 21-year old patient in whom severe neuropathic pain developed after vincristine treatment. Findings: The patient was a CYP3A5 nonexpressor and presented with reduced CYP3A4/5 functional activity, a likely reason for the occurrence of the adverse event, as genotyping showed that his status was wild type for the ABCB1 and CEP72 genes. Implications: CYP phenotype and genotype may explain the occurrence of severe neuropathy in some patients treated with vincristine. (C) 2016 Elsevier HS Journals, Inc. All rights reserved.
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