论文部分内容阅读
目的:研究尿苷二磷酸葡萄糖醛酸转移酶(uridine-5’-diphosphate glucuronosyl transferase,UGTs)基因多态性对米格列奈在中国人体内药代动力学个体差异的影响,为临床制定合理的用药方案提供依据。方法:健康受试者单次和多次给药米格列奈片,测定其血药浓度并计算药代动力学参数,同时检测分析UGT1A3和UGT2B7基因多态性。按不同基因型分组,组间药代动力学参数的比较应用单因素方差分析和二独立样本t检验,组间多重差异比较采用LSD-t检验。结果:单次给药后米格列奈药代动力学参数个体差异与UGT1A3和UGT2B7基因多态性间相关性经方差分析和独立样本t检验P>0.05,不存在相关性;多次给药后米格列奈的药代动力学参数个体差异与UGT1A3基因多态性间相关性经方差分析,FAUC=11.279,PAUC=0.001,FCL=16.712,PCL=0.001,差异显著,表明UGT1A3代谢米格列奈的酶活性为UGT1A3*2/*4>UGT1A3*1/*3>UGT1A 3*1/*1>UGT1A3*1/*2>UGT1A3*1/*5;多次给药UGT2B7-1的药代动力学参数FAUC=3.980,PAUC=0.027,FCL=4.433,PCL=0.018,差异显著,表明UGT2B7-1基因代谢米格列奈的酶活性为T/T>G/T>G/G。单次或多次给药,UGT2B7-2基因型与米格列奈药代动力学个体差异间无相关性(P均>0.05)。结论:UGT1A3和UGT2B7-1基因多态性对米格列奈体内代谢动力学个体差异有显著影响;UGT2B7-2基因多态性与米格列奈体内代谢动力学个体差异间不存在相关性。
OBJECTIVE: To study the effect of uridine-5’-diphosphate glucuronosyl transferase (UGTs) gene polymorphism on the individual differences in the pharmacokinetics of mitiglinide in Chinese. Medication program to provide the basis. Methods: Healthy subjects were given single and multiple doses of mitochondrial tablets, plasma concentrations were measured and pharmacokinetic parameters were calculated. Meanwhile, UGT1A3 and UGT2B7 gene polymorphisms were detected. Grouping by different genotypes, one-way ANOVA and two independent samples t test were used to compare pharmacokinetic parameters between groups. LSD-t test was used to compare multiple differences among groups. RESULTS: The correlation between individual differences in the pharmacokinetic parameters of mitiglinide and the polymorphisms of UGT1A3 and UGT2B7 after single administration was not significant by ANOVA and independent samples t-test (P> 0.05). Multiple administrations The correlation between post-mitiglinide pharmacokinetic parameters and UGT1A3 gene polymorphism was analyzed by ANOVA, FAUC = 11.279, PAUC = 0.001, FCL = 16.712 and PCL = 0.001, showing significant difference The enzyme activity of lenecone was UGT1A3 * 2 / * 4> UGT1A3 * 1 / * 3> UGT1A3 * 1 / * 1> UGT1A3 * 1 / * 2> UGT1A3 * 1 / * 5; Pharmacokinetic parameters FAUC = 3.980, PAUC = 0.027, FCL = 4.433, PCL = 0.018, significant difference, indicating that UGT2B7-1 gene metabolism mitochondrial enzyme activity T / T> G / T> G / G. There was no correlation between UGT2B7-2 genotype and individual differences in the pharmacokinetics of mitiglin (P> 0.05). CONCLUSION: The UGT1A3 and UGT2B7-1 gene polymorphisms have a significant effect on the individual differences of mitochondrial metabolisms in vivo. There is no correlation between UGT2B7-2 gene polymorphism and individual differences of mitiglinide in vivo.