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目的探索细胞色素P450 3A4(CYP3A4),CYP3A5基因多态性与卡马西平浓度与皮肤药物不良反应(ADR)的相关性。方法对67例口服卡马西平治疗的患者的卡马西平血药浓度、CYP3A4*18、CYP3A4*18B、CYP3A5*3、CYP3A4*1B位点基因型进行测定。比较不同基因型组间卡马西平血药浓度、剂量校正浓度、标准化浓度的差异。同时观察患者是否发生卡马西平相关的皮肤ADR。结果 CYP3A4*18位点*1/*1型和*1/*18型患者分别为63例(94.03%)和4例(5.97%),2组患者的卡马西平血药浓度分别为(6.77±2.11),(5.26±1.05)μg·m L~(-1);剂量校正浓度分别为(10.68±5.12),(9.63±4.19)μg·m L~(-1);标准化浓度(0.31±0.25),(0.26±0.13)μg·m L~(-1),差异均无统计学意义(P>0.05)。CYP3A4*18B位点*1/*1型、*18B/*18B型和*1/*18B型患者分别为37例(55.22%)、4例(5.97%)和26例(38.81%),3组患者的卡马西平血药浓度(6.78±2.35),(4.81±1.19),(6.82±1.68)μg·m L~(-1);剂量校正浓度(10.72±6.06),(9.68±4.19),(10.61±3.50)μg·m L~(-1);标准化浓度(0.30±0.25),(0.29±0.15),(0.32±0.24)μg·m L~(-1),差异均无统计学意义(P>0.05)。CYP3A5*3位点*1/*1型、*3/*3型和*1/*3型患者分别为3例(4.48%)、32例(47.76%)和32例(47.76%),3组患者的卡马西平血药浓度(4.51±1.25),(6.95±2.19),(6.61±1.97)μg·m L~(-1);剂量校正浓度(9.73±5.13),(10.25±5.51),(11.07±4.67)μg·m L~(-1);标准化浓度(0.28±0.18),(0.27±0.21),(0.35±0.27)μg·m L~(-1),差异均无统计学意义(P>0.05)。观察期内均未发现与卡马西平相关的皮肤ADR。结论本研究未能发现CYP3A4*18、CYP3A4*18B、CYP3A5*3位点的基因多态性与卡马西平浓度以及皮肤ADR的明显相关性,可能与样本量较少有关。
Objective To explore the relationship between CYP3A4, CYP3A5 gene polymorphism and the concentration of carbamazepine and adverse drug reaction (ADR) in skin. Methods The plasma concentration of carbamazepine, CYP3A4 * 18, CYP3A4 * 18B, CYP3A5 * 3 and CYP3A4 * 1B loci were determined in 67 patients treated with carbamazepine. The differences of plasma concentration of carbamazepine, dose-corrected concentration and normalized concentration among different genotype groups were compared. Simultaneous observation of whether patients with carbamazepine skin associated with ADR. Results The CYP3A4 * 18 locus * 1 / * 1 and * 1 / * 18 patients were 63 (94.03%) and 4 (5.97%) patients respectively. The plasma concentration of carbamazepine in CYP3A4 * ± 2.11) and (5.26 ± 1.05) μg · m L -1, respectively. The dose-corrected concentrations were (10.68 ± 5.12) and (9.63 ± 4.19) μg · m L -1, respectively. 0.25) and (0.26 ± 0.13) μg · m L -1, respectively, with no significant difference (P> 0.05). 37 cases (55.22%), 4 cases (5.97%) and 26 cases (38.81%) of CYP3A4 * 18B locus * 1 / * 1 type, * 18B / * 18B type and * 1 / * 18B type respectively The plasma concentrations of carbamazepine (6.78 ± 2.35), (4.81 ± 1.19) and (6.82 ± 1.68) μg · m L -1 were significantly higher than those of the control group (10.72 ± 6.06 vs 9.68 ± 4.19, , (10.61 ± 3.50) μg · m L -1; the normalized concentrations (0.30 ± 0.25), (0.29 ± 0.15) and (0.32 ± 0.24) μg · m L -1 had no statistical significance Significance (P> 0.05). 3 (4.48%), 32 (47.76%) and 32 (47.76%) cases of CYP3A5 * 3 locus * 1 / * 1, * 3 / * 3 and * 1 / * 3, respectively The plasma concentrations of carbamazepine (4.51 ± 1.25), (6.95 ± 2.19) and (6.61 ± 1.97) μg · m L -1 were significantly higher than those in the control group (9.73 ± 5.13 and 10.25 ± 5.51, , (11.07 ± 4.67) μg · m L -1; the standardization concentrations were 0.28 ± 0.18, 0.27 ± 0.21 and 0.35 ± 0.27 μg · m L -1, respectively, with no statistical difference Significance (P> 0.05). No skin ADR associated with carbamazepine was observed during the observation period. Conclusion This study failed to find CYP3A4 * 18, CYP3A4 * 18B, CYP3A5 * 3 locus genetic polymorphism and carbamazepine concentration and skin ADR significant correlation may be related to the sample size less relevant.