Influence of CYP3A5*3 and ABCB1 C3435T on clinical outcomes and trough plasma concentrations of imatinib in Nigerians with chronic myeloid leukaemia

• DOI: 10.1111/jcpt.12424
• Publication Date: 2016-07-18T08:37:17Z
• Authors: B. A. Adeagbo; O. O. Bolaji; T. A. Olugbade; M. A. Durosinmi; R. A. Bolarinwa; C. Masimirembwa
• Keywords: Nigerians; Imatinib Mesylate

Imatinib mesylate is the first-line drug for treatment of Philadelphia/bcr-abl positive chronic myeloid leukaemia (CML). It known to be metabolized mostly by CYP3A4 and CYP3A5 isoforms while its efflux mediated transporters ABCB1 ABCG2. Genetic polymorphism some these enzymes have been linked with inter-individual variations in pharmacokinetics drug. This study, therefore, investigated influence CYP3A5*3, ABCG2 421C>A 3435 C>T genetic on clinical outcome steady-state trough plasma concentration (TPC) imatinib Nigerians CML.A total 110 CML each whom had receiving a 400 mg daily dose at least 1 month were genotyped C>T. The TPC all patients determined validated HPLC method possible relationships between genotypes, age, outcome, sex, ethnicity analysed.Subjects TT genotype C3435T higher frequencies complete haematological response (CHR), cytogenetic (CCR) major molecular (MMR) but not statistically significant (P < 0·05). No was observed. However, associations observed various genotypes both CYP3A5*3 0·001) 0·001). GG C3435T, respectively, TPC.This first pharmacogenetics study Nigerian population ethnic differences distribution C3435T. polymorphisms are associated this population.