比较空腹及餐后雷贝拉唑钠肠溶微丸型胶囊的人体生物利用度

目的:评价空腹和餐后两种状态下口服雷贝拉唑钠肠溶微丸型胶囊的人体生物利用度。方法:22位健康志愿受试者随机分成2组,每组11人,分别空腹或餐后口服给予雷贝拉唑钠肠溶微丸型胶囊或雷贝拉唑钠肠溶片各20 mg,7 d清洗后交叉给药。采用高效液相色谱-串联质谱(HPLC/MS/MS)法测定血浆中雷贝拉唑的血药浓度。结果:空腹口服雷贝拉唑钠肠溶微丸型胶囊与雷贝拉唑钠肠溶片的主要药动学参数如下:t_1/2分别为(2.75±1.14)h和(2.57±1.03)h;T_max(2.57±1.04)h和(3.14±1.09)h;C_max分别为(372.55±169.10)ng·ml^-1和(386.35±174.14)ng·ml^-1;AUC_0→t分别为(955.98±586.10)ng·h·ml^-1和(918.84±445.69)ng·h·ml^-1;AUC_0→∞(978.14±610.44)ng·h·ml^-1和(946.6±473.30)ng·h·ml^-1。MRT_0→t分别为(3.85±1.11)h和(4.59±1.28)h; MRT_0→∞分别为(4.12±1.26)h和(4.92±1.56)h;V_d分别为(100.38±51.26)L· kg^-1和(60.81±61.20)L·kg^-1。空腹状态下给药的相对生物利用度F为(113.2±59.6)%。餐后口服雷贝拉唑钠肠溶微丸型胶囊与雷贝拉唑钠肠溶片的主要药动学参数如下:t_1/2分别为(2.47±0.69)h和(1.94±0.65)h;T_max(3.27±0.80)h和(4.50±1.13)h;C_max分别为(404.00±134.38)ng·ml^-1和(410.14±126.98)ng·ml^-1;AUC_0→t分别为(969.66±372.63)ng·h·ml^-1和(998.71±443.56)ng·h·ml^-1;AUC_0→∞分别为(984.97±385.42)ng·h·ml^-1和(1 010.56±455.27)ng·h·ml^-1;MRT_0→t分别为(4.30±0.97)h和(5.50±1.14)h;MRT_0→∞分别为(4.50±1.16)h和(5.62±1.19)h;V_d分别为(84.40±42.11)L· kg^-1和(67.72±41.67)L· kg^-1。餐后给药的相对生物利用度F为(118.1±94.1)%。统计学检验结果表明空腹及餐后给药两制剂间具有生物等效性。试验药组的T_max在空腹状态下相比参比药组略快,但无显著性差异(P>0.05),而在餐后状态下,试验药组T_max更快,且有显著性差异(P<0.05)。空腹及餐后两种状态下试验药组V_d较参比药V_d均有显著性差异(P<0.05)。结论:空腹及餐后两种状态下口服雷贝拉唑钠肠溶微丸型胶囊其弥散程度较高、释放药物较快、吸收迅速,用餐对药物的释放及生物利用度的影响较小。

Comparison of bioavailabilities of rabeprazole sodium enteric-coated pellets capsules under fasting and fed state

OBJECTIVE To evaluate bioavailabilities of rabeprazole sodium enteric-coated pellets capsules under both fasting and fed state.METHODS A total of 22 healthy volunteers were randomly divided into two groups and given with a single oral dose of 20 mg rabeprazole sodium enteric-coated pellets capsules or rabeprazole sodium enteric-coated tablets respectively under fasting or fed conditions. Wash period was 7 days. Blood samples were collected at different time points. Plasma concentrations of rabeprazole were determined by LC/MS/MS method.RESULTS Main pharmacokinetic parameters of two formulations under fasting state were shown as follows: t_1/2 were (2.75±1.14)h and (2.57±1.03)h. T_max (2.57±1.04)h and (3.14±1.09)h. C_max were (372.55±169.10) ng·ml^-1 and (386.35±174.14) ng·ml^-1. AUC_0→t were (955.98±586.10) ng·h·ml^-1 and (918.84±445.69) ng·h·ml^-1. AUC_0→∞ were (978.14±610.44) ng·h·ml^-1 and (946.62±473.30) ng·h·ml^-1. MRT_0→t were (3.85±1.11) h and (4.59±1.28) h. MRT_0→∞were (4.12±1.26) h and (4. 92±1.56) h. V_d were (100.38±51.26) L· kg^-1 and (60.81±61.20) L· kg^-1. Compared with reference formulation, relative bioavailability of test preparation was (113.2±59.6)%. Main pharmacokinetic parameters of two formulations under fed conditions were shown as follows: t_1/2were (2.47±0.69) h and (1.94±0.65) h. T_max(3.27±0.80) h and (4.50±1.13) h. C_max were (404.00±134.38) ng·ml^-1 and (410.14±126.98) ng·ml^-1. AUC_0→t were (969.66±372.63) ng·h·ml^-1 and (998.71±443.56) ng·h·ml^-1. AUC_0→∞ were (984.97±385.42) ng·h·ml^-1 and (1010.56±455.27) ng·h·ml^-1. MRT_0→t were (4.30±0.97) h and (5.50±1.14) h. MRT_0→∞ were (4.50±1.16) h and (5.62±1.19) h. V_d were (84.40±42.11) L· kg^-1 and (67.72±41.67) L·kg^-1. Relative bioavailability of test preparation was (118.1±94.1)%. Results showed that two formulations were bioequivalent under both fasting and fed states. Under fasting state, T_max of test drug was slightly faster than reference drug, but had no significant difference (P>0.05). Under fed state, T_max of test drug was faster than reference formulation, and there was a significant difference (P<0.05). Under both fasting and fed states, there was a significant difference in V_d between test and reference drugs.CONCLUSION Rabeprazole sodium enteric-coated pellets capsules have a good bioavailability with high degree of dispersion, can release drug rapidly and be absorbed well. Food have little effects on drug release and bioavailability.