泮托拉唑钠在健康人体内的相对生物利用度及生物等效性研究

Pharmacokinetics and relative bioavailability and bioequialence of Pantoprazole Sodium Enteric-Coated Tablet in healthy volunteer

目的建立测定血浆中泮托拉唑的高效液相色谱内标法并研究泮托拉唑钠肠溶片的相对生物利用度及生物等效性。方法 20名健康男性试验者随机分为两组,分别单剂量口服泮托拉唑钠肠溶片试验制剂或参比制剂40 mg,于服药前(0 h)和服药后0.75、1.0、1.5、2.0、2.5、3.0、3.5、4.0、5.0、6.0、8.0、10.0、12.0 h抽取静脉血。7 d清洗期后再交叉给药。采用高效液相色谱法测定血浆中泮托拉唑的浓度。通过WinNonlin 5.2.1数据统计软件计算主要药动学参数,评价两制剂的生物等效性。结果受试制剂与参比制剂血浆中泮托拉唑片的t1/2:(1.83±0.56)h、tmax:(2.80±0.62)h、Cmax:(2985.6±641.2)ng/mL、AUC0-t:(9682±4478)ng.h/mL;参比制剂的t1/2:(1.96±0.52)h、tmax:(2.90±0.85)h、Cmax:(3231.4±923.5)ng/mL、AUC0-t:(9388±4125)ng.h/mL。以AUC0-t计算,与参比制剂相比受试制剂中泮托拉唑的相对生物利用度为(104.9±26.1)%。结论泮托拉唑钠肠溶片试验制剂与参比制剂在健康人体内具有生物等效性。

Objective To evaluate the bioavailability and bioequivalence of two formulation of Pantoprazole Enter- Coated Tablet in healthy volunteers. Methods Single oral dose of two Pantoprazole Sodium Enteric-Coated Tablets were given to 20 healthy volunteers in a randomized 2-way cross-over study. The blood samples were collected at 0 h, and 0.75, 1.0, 1.5, 2.0, 2.5, 3.0,3.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 h after taking 40 mg of Pantoprazole Sodium Enter- ic-Coated Tablet test preparation and preparation, and with repeated sampling of the crossover drug administration 7 d after clearance. The concentrate toprazole in plasma Pantoprazole was determined by HPLC. The pharmaeokinetie pa- rameters were calculated and compared statistically to evaluate the relative bioequivalenee between the two prepara- tions of pantoparazole sodium by WinNonlin 5.2.1 software. Results The major pharmaeokinetic parameters of two Pantoprazole Sodium Enteric-Coated Tablets test preparation and reference preparation were as follows, t1/2： （1.83± 0.56） h, tmax： （2.80±0.62） h, Cmax： （2985.6±641.2） ng/mL, A UC0-1： （9682±4478） ng h/mL, t1/2： （1.96±0.52） h, tmax： （2.90± 0.85） h, Cmax： （3231.4±923.5） ng/mL, A UC0-1： （9388±4125） ng-h/mL, respectively. The relative bioavailability of test preparation was （104.9±26.1）%. Conclusion Statistical analysis showes Pantoprazole Sodium Enteric-Coated Tablets test preparation and reference preparation are bioequivalent in Chinese healthy volunteers.