醋酸泼尼松片在中国人体内的药动学研究

Pharmacokinetics of prednisone acetate tablets in Chinese volunteers

目的研究醋酸泼尼松在中国人体内的药动学。方法采用随机开放、双周期交叉、单剂量、空腹给药试验,给予16名受试者醋酸泼尼松片(5 mg)和泼尼松龙片(5 mg),采集不同时间点的血样,利用LC-MS/MS法测定泼尼松和泼尼松龙血药浓度,计算其药动学参数,并对数据进行整理分析。结果醋酸泼尼松片体内泼尼松龙药动学参数t_(max)、C_(max)、AUC_(0~t)、AUC_(0~∞)值分别为1.25 h、(153.41±24.99)ng·mL^(-1)、(655.70±126.05)ng·h·mL^(-1)、(683.44±129.16)ng·h·mL^(-1),泼尼松的药动学参数分别为2.50 h、(27.65±4.693)ng·mL^(-1)、(145.32±20.67)ng·h·mL^(-1)、(153.42±23.14)ng·h·mL^(-1);泼尼松龙片体内泼尼松龙药动学参数分别为0.75 h、(178.73±37.64)ng·mL^(-1)、(738.63±169.30)ng·h·mL^(-1)、(766.04±172.64)ng·h·mL^(-1),泼尼松药动学参数分别为2.50 h、(28.95±3.58)ng·mL^(-1)、(157.84±14.48)ng·h·mL^(-1)、(166.30±17.73)ng·h·mL^(-1)。两制剂体内经过折算后泼尼松龙药动学参数C_(max)、AUC_(0~t)、AUC_(0~∞)的几何均值比值分别为96.17%、99.17%、99.66%,C_(max)、AUC_(0~t)、AUC_(0~∞)的90%置信区间分别为87.73%~105.42%、95.90%~102.55%、96.19%~103.27%;泼尼松药动学参数C_(max)、AUC_(0~t)、AUC_(0~∞)的几何均值比值分别为105.27%、101.65%、101.88%,C_(max)、AUC_(0~t)、AUC_(0~∞)的90%置信区间分别为98.88%~112.09%、97.54%~105.94%、97.90%~106.02%。结论醋酸泼尼松片与泼尼松龙片经过折算后的C_(max)、AUC_(0~t)、AUC_(0~∞)的90%置信区间均在可接受范围内;等剂量(摩尔数)醋酸泼尼松片和泼尼松龙片在中国人体内血浆药物具有生物等效性。

Objective To determine the pharmacokinetics of prednisone acetate in Chinese volunteers.Methods A randomized open-ended,double-cycle crossover,single-dose,fasting administration trial was designed for towards to 16 subjects:prednisone acetate tablets(5 mg)and prednisolone tablets(5 mg).The blood drug concentrations were measured at different time points with LC-MS/MS and then the data analyzed to calculate the pharmacokinetic parameters.Results The pharmacokinetic parameters t_(max),C_(max),AUC_(0~t) and AUC_(0~∞)of prednisolone in the prednisone acetate tablets were 1.25 h,(153.41±24.99)ng·mL^(-1),(655.70±126.05)ng·h·mL^(-1) and(683.44±129.16)ng·h·mL^(-1),while of prednisone were 2.50 h,(27.65±4.693)ng·mL^(-1),(145.32±20.67)ng·h·mL^(-1),and(153.42±23.14)ng·h·mL^(-1),respectively.The pharmacokinetic parameters t_(max),C_(max),AUC_(0~t) and AUC_(0~∞)values of the prednisolone in prednisolone tablets were 0.75 h,(178.73±37.64)ng·mL^(-1),(738.63±169.30)ng·h·mL^(-1),and(766.04±172.64)ng·h·mL^(-1),while of the prednisone were 2.50 h,(28.95±3.576)ng·mL^(-1),and(157.84±14.48)ng·h·mL^(-1) and(166.30±17.73)ng·h·mL^(-1).The geometric mean ratios of the prednisone pharmacokinetic parameters C_(max),AUC_(0~t),and AUC_(0~∞)after the conversion of prednisone acetate tablets and prednisolone tablets in vivo were 96.17%,99.17%,and 99.66%.The 90%confidence intervals of C_(max),AUC_(0~t),and AUC_(0~∞)were 87.73%~105.42%,95.90%~102.55%,and 96.19%~103.27%,respectively.While the geometric mean ratios of the prednisolone pharmacokinetic parameters C_(max),AUC_(0~t),and AUC_(0~∞)were 105.27%,101.65%,and 101.88%and the 90%confidence intervals of C_(max),AUC_(0~t),and AUC_(0~∞)were 98.88%~112.09%,97.54%~105.94%,and 97.90%~106.02%,respectively.Conclusion After the convertion,the 90%confidence intervals of C_(max),AUC_(0~t) and AUC_(0~∞)of prednisone acetate tablets and prednisolone tablets in vivo are within acceptable range.Equal doses(number of moles)of prednisone acetate tablets and prednisolone tablets are bioequivalent in Chinese volunteers.