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

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. Th...

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Bibliographic Details
Published in:Leukemia & lymphoma 2019-01, Vol.60 (1), p.216-221
Main Authors: Adehin, Ayorinde, Adeagbo, Babatunde A., Kennedy, Martin A., Bolaji, Oluseye O., Olugbade, Tiwalade A., Bolarinwa, Rahman A., Durosinmi, Muheez A.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - therapeutic use
Biological Variation, Population - genetics
Biotransformation
chronic myeloid leukemia
CYP1A2
CYP2C8
CYP2C9
CYP3A5
Cytochrome P-450 CYP1A2 - genetics
Cytochrome P-450 CYP1A2 - metabolism
Cytochrome P-450 CYP2C8 - genetics
Cytochrome P-450 CYP2C8 - metabolism
Cytochrome P-450 CYP2C9 - genetics
Cytochrome P-450 CYP2C9 - metabolism
Cytochrome P-450 CYP3A - genetics
Cytochrome P-450 CYP3A - metabolism
Female
Humans
Imatinib
Imatinib Mesylate - pharmacokinetics
Imatinib Mesylate - therapeutic use
Leukemia, Myeloid, Chronic-Phase - drug therapy
Leukemia, Myeloid, Chronic-Phase - genetics
Male
Middle Aged
Nigeria
Polymorphism, Single Nucleotide
Prospective Studies
Young Adult
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Summary: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.
ISSN:1042-8194
1029-2403
DOI:10.1080/10428194.2018.1466291