利培酮分散片和普通片在健康人体的药动学比较

Pharmacokinetic comparison of dispersible and conventional tablet formulations of risperidone in healthy volunteers

目的比较利培酮分散片和普通片在健康人体的药动学。方法采用自身交叉对照试验设计,20名健康受试者在不同周期分别口服利培酮分散片和普通片各2 mg,采用高效液相色谱-串联质谱法测定血浆中利培酮和9-羟基利培酮浓度。应用DAS2.1.1软件进行药动学参数计算及生物等效性评价。结果利培酮普通片和分散片的利培酮主要药动学参数如下:ρ_(max)分别为(14.03±6.54)和(13.77±7.73)μg·L^(-1),t_(max)分别为(1.36±0.71)和(1.17±0.81)h,t_(1/2)分别为(3.59±1.69)和(3.87±1.78)h,AUC_(0-t)分别为(66.02±46.79)和(73.05±59.85)μg·h·L^(-1),AUC_(0-∞)分别为(71.26±48.00)和(78.97±63.48)μg·h·L^(-1)。利培酮普通片和分散片的9-羟基利培酮的ρ_(max)分别为(8.53±3.63)和(8.50±2.92)μg·L^(-1),t_(max)分别为(4.54±4.19)和(5.75±3.36)h,t_(1/2)分别为(17.97±4.00)和(17.34±4.44)h,AUC_(0-t)分别为(196.89±61.78)和(198.01±61.56)μg·h·L^(-1),AUC_(0-∞)分别为(220.55±65.36)和(218.58±65.85)μg·h·L^(-1)。结论利培酮分散片和普通片的药动学无显著差异,且两制剂具有生物等效性。

AIM To compare the pharmacokinetic properties of dispersible and conventional tablet of risperidone in Chinese healthy volunteers. METHODS The clinical investigation was designed asa randomized and crossover study. A single oral dose （2 mg） of risperidone in either formulation was given to 20 healthy volunteers. The concentrations of risperidone and 9- hydroxy- risperidone （9- OH- RIP） in plasma were determined by HPLC- MS method. RESULTS The main pharmacokinetic parameters of risperidone of conventional and dispersible tablets were as follows： Pmax were （14.03 ± 6.54） and （13.77 ± 7.73） μg.L^-1, tmax were （1.36 ± 0.71） and （1.17 ± 0.81） h, t1/2 were （3.59 ± 1.69） and （3.87 ± 1.78） h, AUC0-t were （66.02 ± 46.79） and （73.05 ± 59.85） μg.h.L^-1, AUC0-00, were （71.26 ± 48.00） and （78.97 ± 63.48） μg.h.L^-1, respectively. The main pharmacokinetic parameters of 9-OH-RIP of two risperidone tablets were as follows： pmaxwere （8.53 ± 3.63） and （8.50 ± 2.92） μg.L^-1, tmax were （4.54 ± 4.19） were （5.75 ± 3.36） h, t1/2 were （ 17.97 ± 4.00） and （ 17.34 ± 4.44） h, AUCo-t, were （ 196.89 ± 61.78） and （ 198.01 ± 61.56） μg.h.L^-l, AUCo-oo were （220.55 ± 65.36） and （218.58 ± 65.85） μg.h〉L^-1, respectively. CONCLUSION The dispersible and conventional tablets of risperidone are bioequivalent in human body.