Slanar O, Drazd'áková M, Babiárová K, Pechandová K, Buzková H, Perlík F, Zima T
Ustav klinické biochemie a laboratorní diagnostiky 1. LF UK a VFN, Praha 2 0dd4lenf klinicke farmakologie 1. LF UK a VFN, Praha.
Cas Lek Cesk. 2007;146(9):708-11.
Polymorphisms in drug metabolizing enzymes are considered as a major factor influencing the incidence of adverse drug reactions or failure of pharmacotherapy. Our aim was to compare the distribution of functional polymorphisms in the genes CYP2D6 and CYP2C19 between healthy control group and of patients reffered to our department due to adverse drug reactions or insufficient efficacy of a treatment.
The group of patients comprised of 60 subjects, 218 healthy unrelated subjects were included in the cotrol group. In both groups genotypes of CYP2D6 and CYP2C19 were analyzed. There were significantly fewer extensive metabolizers of CYP2D6 in the patient group comparison with healthy control subjects (25.0% vs. 49.8%) while the proportion of intermediate metabolizers was significantly higher than in helthy population (58.3% vs. 38.5%). We also observed more poor metabolizers than in control group (13.3% vs. 6.8%), but the difference did not reach level of statistical significance probably due to low number of subjects. The distribution of either ultrarapid metabolizers of CYP2D6 or deficient alleles of CYP2C19 was similar in both groups.
Clinically apparent alteration of drug effects are often caused by partial or complete deficit of CYP2D6 activity. Our results confirm the importance of CYP2D6 polymorphisms on the efficycy and safety of pharmacotherapy.
药物代谢酶的多态性被认为是影响药物不良反应发生率或药物治疗失败的主要因素。我们的目的是比较健康对照组与因药物不良反应或治疗效果不佳而转诊至我科的患者组中CYP2D6和CYP2C19基因功能多态性的分布情况。
患者组包括60名受试者,对照组纳入218名健康无关受试者。对两组的CYP2D6和CYP2C19基因型进行分析。与健康对照受试者相比,患者组中CYP2D6的广泛代谢者明显较少(25.0%对49.8%),而中间代谢者的比例明显高于健康人群(58.3%对38.5%)。我们还观察到,与对照组相比,代谢不良者更多(13.3%对6.8%),但由于受试者数量较少,差异未达到统计学意义水平。两组中CYP2D6的超快代谢者或CYP2C19的缺陷等位基因分布相似。
临床上明显的药物效应改变通常是由CYP2D6活性部分或完全缺乏引起的。我们的结果证实了CYP2D6多态性对药物治疗有效性和安全性的重要性。