Inter-individual variation in imatinib disposition: any role for prevalent variants of CYP1A2, CYP2C8, CYP2C9, and CYP3A5 in Nigerian CML patients?

Abstract	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 CYP2C82 while diminished imatinib levels were seen in two homozygous carriers of CYP3A57. 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.
Authors	Ayorinde Adehin, Babatunde A Adeagbo, Martin A Kennedy, Oluseye O Bolaji, Tiwalade A Olugbade, Rahman A Bolarinwa, Muheez A Durosinmi
Journal	Leukemia & lymphoma (Leuk Lymphoma) Vol. 60 Issue 1 Pg. 216-221 (01 2019) ISSN: 1029-2403 [Electronic] United States
PMID	29741432 (Publication Type: Journal Article)
Chemical References	Antineoplastic Agents Imatinib Mesylate CYP2C9 protein, human Cytochrome P-450 CYP2C9 CYP1A2 protein, human CYP2C8 protein, human CYP3A5 protein, human Cytochrome P-450 CYP1A2 Cytochrome P-450 CYP2C8 Cytochrome P-450 CYP3A
Topics	Adolescent Adult Aged Antineoplastic Agents (pharmacokinetics, therapeutic use) Biological Variation, Population (genetics) Biotransformation Cytochrome P-450 CYP1A2 (genetics, metabolism) Cytochrome P-450 CYP2C8 (genetics, metabolism) Cytochrome P-450 CYP2C9 (genetics, metabolism) Cytochrome P-450 CYP3A (genetics, metabolism) Female Humans Imatinib Mesylate (pharmacokinetics, therapeutic use) Leukemia, Myeloid, Chronic-Phase (drug therapy, genetics) Male Middle Aged Nigeria Polymorphism, Single Nucleotide Prospective Studies Young Adult

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