本文關(guān)鍵詞： 泮托拉唑 P糖蛋白 多態(tài)性 單核苷酸 藥動學(xué)　出處：《中國新藥與臨床雜志》2017年05期 　論文類型：期刊論文

【摘要】：目的探討健康志愿者的多藥耐藥基因(MDR1)C3435T基因多態(tài)性對泮托拉唑藥動學(xué)的影響。方法用聚合酶鏈反應(yīng)限制性片段長度多態(tài)性分析(PCR-RFLP)法對32例健康受試者進(jìn)行MDR1基因分型,使用高效液相色譜-串聯(lián)質(zhì)譜法測定健康受試者單次空腹口服泮托拉唑腸溶片40 mg后不同時(shí)間點(diǎn)的泮托拉唑血漿濃度,計(jì)算藥動學(xué)參數(shù)并比較3種不同基因型藥動學(xué)參數(shù)間的差異。結(jié)果 MDR1C3435T C/C型、C/T型和T/T型基因型的分布頻率分別為43.8%、40.6%和15.6%,主要的藥動學(xué)參數(shù)ρmax分別為(3.06±0.87)、(2.80±0.83)和(3.52±1.07)μg·m L~(-1),tmax分別為(3.33±1.14)、(2.97±0.75)和(2.13±0.65)h,t_(1/2)分別為(2.38±2.37)、(1.46±0.26)和(2.87±3.25)h,AUC_(0-15)分別為(9.37±7.88)、(6.33±2.20)和(11.01±11.32)μg·h·m L~(-1),AUC0-∞分別為(11.24±12.42)、(6.36±2.21)和(14.21±18.35)μg·h·m L~(-1)。C/C型和C/T型比較各參數(shù)間無顯著差異(P0.05),C/C型和T/T型比較t_(max)、AUC_(0-max)差異顯著(P0.05),C/T型和T/T型比較t_(max)差異顯著(P0.05),其余藥動學(xué)參數(shù)均無顯著差異(P0.05)。結(jié)論 MDR1基因多態(tài)性對泮托拉唑吸收速度和達(dá)峰前吸收程度有顯著影響,但對總暴露量沒有影響。
[Abstract]:Objective to investigate the effect of multidrug resistance (MDR1) C3435T gene polymorphism on pharmacokinetics of pam Tora in healthy volunteers. Methods Polymerase chain reaction (PCR) restriction fragment length polymorphism (PCR) was used to analyze the pharmacokinetics of Pam Tora. MDR1 genotyping was performed in 32 healthy subjects by PCR-RFLP. The plasma concentration of pam Tora was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS) at different time points after a single fasting oral administration of Pam Tora Zol enteric-coated tablets (40 mg). The pharmacokinetic parameters were calculated and the differences of pharmacokinetic parameters among three genotypes were compared. Results MDR1C3435T C / C genotype. The distribution frequencies of C / T and T / T genotypes were 43.6% and 15.6%, respectively. The main pharmacokinetic parameters 蟻 max were 3.06 鹵0.87). The tmax was 3.33 鹵1.14 渭 g 路mL ~ (-1) and 3.52 鹵1.07 渭 g 路mL ~ (-1), respectively. 2. 97 鹵0. 75) and 2. 13 鹵0. 65 hind tit / 2) were 2.38 鹵2. 37) respectively. 1.46 鹵0.26) and 2.87 鹵3.25 hAUC (0-15) were 9.37 鹵7.88). 6.33 鹵2.20) and 11.01 鹵11.32 渭 g 路h 路mL ~ (-1) AUC0- 鈭，

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