泮托拉唑在不同CYP2C19基因型国人体内的药动学

Pharmacokinetics of Pantoprazole in Chinese Healthy Subjects in Relation to CYP2C19 Genotypes

目的研究CYP2C19基因型对泮托拉唑中国健康志愿者体内药动学的影响。方法采用聚合酶链限制性片断长度多态性(PCR-RFLP)分析CYP2C19基因型。24名健康志愿者按照基因型划分的基因表型被随机分为3组(每组8名),纯合子强代谢型组(homEMs),杂合子强代谢型组(hetEMs),弱代谢型组(PMs)。受试者单剂量po40mg泮托拉唑肠溶片后血药浓度的测定采用高效液相色谱法。结果HomEMs,hetEMs,PMs3组个体内的泮托拉唑的主要药动学参数如下:ρmax为(2551.8±1035.2),(3316.63±1237.27)和(4256.04±573.47)μg.L-1;tmax为(3.38±0.92),(3.25±1.54)和(3.50±0.96)h;t1/2Ke为(1.82±1.71),(1.34±0.22)和(5.83±3.28)h;AUC0～t为(5616.37±1878),(8132.22±3549.4)和(24882.71±7051.33)μg.h.L-1;AUC0～∞为(5699.5±1932.1),(8238.5±3513.3)和(32394.9±12428.3)μg.h.L-1。HetEM组和PM组的受试者其泮托拉唑的ρmax高于homEM组(P<0.01),PM组的t1/2Ke要长于homEM组(P<0.01)。AUC0～t和AUC0～∞在PM组要分别高于homEM组和hetEM组(P<0.01),但在homEM组和hetEM组之间没有差异。结论泮托拉唑药动学在个体之间的差异与CYP2C19的基因型有关。

OBJECTIVE To investigate the pharmacokinetics of pantoprazole in healthy Chinese subjects in relation to CYP2C19 genotype status. METHODS The CYP2C19 genotype status of healthy Chinese volunteers was determined by the polymerase chain reaction-restriction fragment length polymorphism technique. Twenty-four healthy subjects were distributed into three groups as extensive metabolizers group （homEMs）, heterozygous extensive metabolizers group （hetEMs）, poor metabolizers （PMs） group. Each group consisted of eight volunteers. After a single oral dose of 40 mg pantoprazole enterie-coater tablet, plasma concentration of pantoprazole was determined by HPLC method. RESULTS The p t t1/2 Ke and AUC0-t of pantoprazole in homEMs group, hetEMs group and PMs group were as follows ： ρmax （2 551.8 ± 1 035.2 ）, （3 316. 63 ± 1 237. 27 ） and （4 256. 04 ± 573.47 ） ug · L^-1, tmax（3.38±0.92）, （3.25±1.54） and （3.50 ±0.96） h, t1/2Ke（1.82±1.71）, （1.34 ±0.22） and （5.83 ±3.28） h, AUC0-t（5 616. 37 ± 1 878）, （8 132. 22±3 549.4） and （24 882. 71 ±7 051.33） ug · L^-1 , AUC0-∞（5 699.5 ± 1 932. 1）, （8 238.5 ±3 513.3） and （32 394. 9 ± 12 428.3）ug · L^-1. The mean ρmax in the hetEM and PM groups were higher than that in the homEM group（P 〈0. 01 ）. The t1/2Ke in PM group was about 3.2 times longer than that in homEM group（P 〈0. 01 ）. The mean AUC0-∞ and mean AUC0-t of PAN were significantly different between the homoEM and PM groups and between the hetEM and PM groups （ P 〈 0. 0 1 ） , but no difference between the homEM and hetEM groups. CONCLUSION Interindividual pharmacokinetic variability of pantoprazole is depended on the genotype of CYP2C19.