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Imatinib has been successful in the management of chronic myeloid leukemia (CML) but some patients experience adverse reactions or develop resistance to its use. The roles of some polymorphisms in genes encoding enzymes critical for the biotransformation of imatinib have been previously examined. This study, hence, evaluated some other unstudied functionally significant polymorphisms in CYP1A2, CYP2C8, CYP2C9, and CYP3A5. Trough imatinib blood levels and genotypes were determined in 42 CML patients by an HPLC-UV technique and a Sequenom iPLEX assay, respectively. Statistical analysis of the influence of genetic polymorphisms on standardized trough level detected no significant relationship. However, higher trough levels were observed in two homozygous carriers of CYP2C8*2 while diminished imatinib levels were seen in two homozygous carriers of CYP3A5*7. The study findings suggest that polymorphisms in drug metabolizing enzymes may be significant for imatinib therapy only in instances where all copies of the relevant studied genes are functionally impaired.

Original publication

DOI

10.1080/10428194.2018.1466291

Type

Journal

Leukemia & lymphoma

Publication Date

01/2019

Volume

60

Pages

216 - 221

Addresses

a Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Obafemi Awolowo University , Ile-Ife , Nigeria.

Keywords

Humans, Leukemia, Myeloid, Chronic-Phase, Cytochrome P-450 CYP1A2, Antineoplastic Agents, Prospective Studies, Biotransformation, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Middle Aged, Nigeria, Female, Male, Cytochrome P-450 CYP3A, Young Adult, Cytochrome P-450 CYP2C9, Cytochrome P-450 CYP2C8, Imatinib Mesylate, Biological Variation, Population