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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:t1/2分别为(2.75±1.14)h和(2.57±1.03)h;Tmax(2.57±1.04)h和(3.14±1.09)h;Cmax分别为(372.55±169.10)ng·ml-1和(386.35±174.14)ng·ml-1;AUC0→t分别为(955.98±586.10)ng·h·ml-1和(918.84±445.69)ng·h·ml-1;AUC0→∞(978.14±610.44)ng·h·ml-1和(946.6±473.30)ng·h·ml-1。MRT0→t分别为(3.85±1.11)h和(4.59±1.28)h;MRT0→∞分别为(4.12±1.26)h和(4.92±1.56)h;Vd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:t1/2分别为(2.47±0.69)h和(1.94±0.65)h;Tmax(3.27±0.80)h和(4.50±1.13)h;Cmax分别为(404.00±134.38)ng·ml-1和(410.14±126.98)ng·ml-1;AUC0→t分别为(969.66±372.63)ng·h·ml-1和(998.71±443.56)ng·h·ml-1;AUC0→∞分别为(984.97±385.42)ng·h·ml-1和(1 010.56±455.27)ng·h·ml-1;MRT0→t分别为(4.30±0.97)h和(5.50±1.14)h;MRT0→∞分别为(4.50±1.16)h和(5.62±1.19)h;Vd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Tmax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Tmax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Vd较参比药Vd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。
OBJECTIVE: To evaluate the bioavailability of oral rabeprazole sodium enteric-coated pellets in both fasting and postprandial states. Methods: Twenty-two healthy volunteers were randomly divided into two groups (11 in each group). The rabbits were given either rabeprazole sodium enteric-coated pellets or rabeprazole sodium enteric-coated tablets, 7 d after the cross-administration of cleaning. Plasma concentrations of rabeprazole were determined by HPLC / MS / MS. Results: The main pharmacokinetic parameters of rabeprazole sodium enteric-coated capsules and rabeprazole sodium enteric-coated tablets were as follows: t1 / 2 were (2.75 ± 1.14) h and (2.57 ± 1.03) h ; Tmax (2.57 ± 1.04) h and (3.14 ± 1.09) h; Cmax were (372.55 ± 169.10) ng · ml-1 and (386.35 ± 174.14) ng · ml-1 respectively; AUC0 → t were (955.98 ± 586.10 ) (918.84 ± 445.69) ng · h · ml-1; AUC0 → ∞ (978.14 ± 610.44) ng · h · ml-1 and (946.6 ± 473.30) ng · h · ml- . MRT0 → t were (3.85 ± 1.11) h and (4.59 ± 1.28) h respectively; MRT0 → ∞ were (4.12 ± 1.26) h and (4.92 ± 1.56) h respectively; Vd was (100.38 ± 51.26) 1 and (60.81 ± 61.20) L · kg-1. The relative bioavailability, F, for fasting administration was (113.2 ± 59.6)%. The main pharmacokinetic parameters of postoperative rabeprazole sodium enteric coated pellets and rabeprazole sodium enteric coated tablets were as follows: t1 / 2 were (2.47 ± 0.69) h and (1.94 ± 0.65) h respectively; Tmax (3.27 ± 0.80) h and (4.50 ± 1.13) h respectively; C max were (404.00 ± 134.38) ng · ml -1 and (410.14 ± 126.98) ng · ml -1, respectively; AUC0 → t were (969.66 ± 372.63) ng · h · ml-1 and (998.71 ± 443.56) ng · h · ml-1 respectively; AUC0 → ∞ were (984.97 ± 385.42) ng · h · ml-1 and (110.56 ± 455.27) ng · h · ml -1; MRT0 → t were (4.30 ± 0.97) h and (5.50 ± 1.14) h respectively; MRT0 → ∞ were (4.50 ± 1.16) h and (5.62 ± 1.19) h respectively; Vd was (84.40 ± 42.11) L · Kg -1 and (67.72 ± 41.67) L · kg -1. The relative bioavailability F after meal administration was (118.1 ± 94.1)%. Statistical tests showed that there was bioequivalence between fasting and postprandial administrations. The Tmax of experimental group was slightly faster than that of the reference group in fasting state, but there was no significant difference (P> 0.05). In the postprandial state, the Tmax of the experimental group was faster and had significant difference (P <0.05). Vd in the fasting and postprandial test groups were significantly different from Vd (P <0.05). Conclusion: The oral rabeprazole sodium enteric-coated pellets under fasting and postprandial conditions have higher diffusion degree, faster release and faster absorption, and have less effect on drug release and bioavailability.