González-Vacarezza Nicolás, Dorado Pedro, Peñas-Lledó Eva M, Fariñas Humberto, Estévez-Carrizo Francisco E, Llerena Adrián
Drug Metabol Drug Interact. 2013;28(3):163-6. doi: 10.1515/dmdi-2013-0008.
P-glycoprotein is an efflux transporter encoded by the multidrug-resistance MDR-1 gene, which influences the absorption and excretion of a variety of drugs. The relation between quetiapine pharmacokinetics and MDR-1 genetic polymorphisms remains controversial. Therefore, the aim of the present study was to analyze the association between quetiapine plasma concentrations and MDR-1 genetic polymorphisms in a bioequivalence trial.
Quetiapine bioequivalence was studied in 24 unrelated healthy Caucasian adults with an open-label, randomized, cross-over, two-sequence and two-period design. Subjects were genotyped for 3435C>T and 1236C>T single-nucleotide polymorphisms. A linear mixed model was performed to compare pharmacokinetic parameters.
Subjects with 3435T/T genotype vs. C carriers showed a higher area under the concentration-time curve from 0 to 36 h (p=0.01). Subjects classified according to 1236C>T SNP and haplotypes showed no statistically significant differences.
These results suggest that the polymorphic MDR-1, in particular the 3435C>T allelic variant, might influence plasma levels of quetiapine.
P-糖蛋白是一种由多药耐药MDR-1基因编码的外排转运蛋白，它影响多种药物的吸收和排泄。喹硫平药代动力学与MDR-1基因多态性之间的关系仍存在争议。因此，本研究的目的是在一项生物等效性试验中分析喹硫平血药浓度与MDR-1基因多态性之间的关联。
采用开放标签、随机、交叉、双序列和双周期设计，对24名无亲缘关系的健康白种成年人进行喹硫平生物等效性研究。对受试者进行3435C>T和1236C>T单核苷酸多态性基因分型。采用线性混合模型比较药代动力学参数。
3435T/T基因型受试者与C等位基因携带者相比，0至36小时的浓度-时间曲线下面积更高（p=0.01）。根据1236C>T单核苷酸多态性和单倍型分类的受试者无统计学显著差异。
这些结果表明，多态性MDR-1，特别是3435C>T等位基因变体，可能影响喹硫平的血药浓度。
