Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia

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Abstract

This study explored the association of 14 single nucleotide polymorphisms (SNPs) in 3 genes coding for influx transporters (SLC22A1, SLCO1B1, andSLCO1B3), 2 genes coding for efflux transporters (ABCB1 and ABCG2), and 4 genes coding for enzymes (CYP2C9, CYP2C19, CYP2D6, and CYP3A5) with the pharmacokinetics of imatinib in Japanese patients with chronic myeloid leukemia (CML). Pharmacokinetic parameters were estimated by a population pharmacokinetic analysis based on 622 plasma samples from 34 patients at steady-state. Approximately 4.6-fold variability in individual clearance was observed (range, 3.4-15.5 L/hr). The individual estimated clearance was significantly increased in patients with SLCO1B3 334GG genotype (median value ± SD, 9.5 ± 3.1 L/hr; n = 19) compared with SLCO1B3 334TT and TG genotypes (7.0 ± 3.1 L/hr; n = 15) (P = 0.019). Patients with ABCB1 3435CC genotype had significantly higher imatinib clearance (12.7 ± 3.0 L/hr; n = 7) compared with patients with ABCB1 3435CT and TT genotypes (7.9 ± 2.7 L/hr; n= 27) (P = 0.035). In conclusion, the present study suggests that SNPs of the influx transporter SLCO1B3 and the efflux transporter ABCB1 were functionally associated with individual variability of imatinib pharmacokinetics in Japanese patients with CML.

Journal

  • Therapeutic Drug Monitoring

    Therapeutic Drug Monitoring 33(2), 244-250, 2011-04-01

    Lippincott Williams & Wilkins

Codes

  • NII Article ID (NAID)
    120005952466
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    0163-4356
  • Data Source
    IR 
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