Search

Purpose: This exploratory study aimed to explain the interindividual variabilities of docetaxel pharmacokinetics and pharmacodynamics in Asian nasopharyngeal carcinoma patients ( n = 54) through the genotyping of CYP3A4, CYP3A5, ABCB1, ABCC2, ABCG2 and SLCO1B3 genes. Methods: Docetaxel was administered over 1 h on days 1, 8, and 15 every 28 days at 30 mg/m/dose. Genomic DNA was isolated from peripheral blood and genotyped for the selected polymorphisms in the candidate genes. Docetaxel pharmacokinetic parameters were estimated by non-compartmental modelling. Results: Patients homozygous for the variant allele (GG) of SLCO1B3 rs11045585 (IVS12-5676A > G) had significantly higher area under the plasma concentration-time curve of docetaxel ( P = 0.026) and lower clearance ( P = 0.036) compared to patients with AA/AG genotypes. Patients harbouring the heterozygous genotype (GA + GT + TA) for ABCB1 rs2032582 (2677G > T/A) had the highest percentage decrease in nadir haemoglobin from cycle 1 baseline compared to those with GG/TT genotypes ( P = 0.006). Similar trend was observed for ABCB1 rs1045642 (3435C > T) with heterozygotes (CT) having the highest percentage decrease in nadir haemoglobin from cycle 1 baseline compared to those with CC/TT genotypes ( P = 0.066). Conclusions: This study suggests that the cooperative influence of functional polymorphisms in SLCO1B3 and ABCB1 genes may be responsible for the interindividual variability in docetaxel disposition in Asian nasopharyngeal cancer patients. [ABSTRACT FROM AUTHOR]