摘要
目的研究健康志愿者单剂量静脉滴注注射用雷贝拉唑钠和口服雷贝拉唑钠肠溶片后的药动学行为，并评价注射用雷贝拉唑钠药动学参数与剂量的相关性。方法将12名健康志愿者进行随机三交叉试验，分别单剂量静脉滴注注射用雷贝拉唑钠20、40、60mg；注射用雷贝拉唑钠试验结束后，经过1个清洗期，12名受试者再次口服20mg雷贝拉唑钠肠溶片，测定给药后10h（或12h）内的血药浓度，用DAS3．0软件计算药动学参数。结果单剂量静脉滴注20、40、60mg注射用雷贝拉唑钠后，雷贝拉唑钠的消除半衰期（t1/2）大约为1～2h，血浆药物浓度（Cmax）随剂量增加呈线性增加（0．9628±0．1321～2．9782±0．4947μg·mL-1）；20—60mg剂量曲线下面积（AUC）也呈线性增加（AUC0-t 1．3247±0．3597～3．9924±1．0μgh·mL-1；AUC0-∞：1．3390±0．3706-4．0410±1．0355μg·h·mL-1）；口服20mg雷贝拉唑钠肠溶片后，雷贝拉唑钠的tmax为3．4±0．8h，t1／2为1．38±0．50h，Cmax为0．5078±0．1798μg·mL-1，AUC0-t 为1．0518±0．4606μg·h·mL-1，AUC0-∞。为1．0641±0．4756μg·h·mL-1。结论静脉滴注注射用雷贝拉唑钠的药动学在20～60mg时剂量呈线性，Cmax、AUC的升高与剂量成正比；不同剂量组间的药动学参数无统计学差异；除20mg剂量组的t1/2性别间存在显著性差异外，其他剂量组的药动学参数性别问均无统计学差异。
OBJECTIVE To study the pharmacokinetics characterization of Rabeprazole in the healthy subjects, and assess the dose proportionality of Rabeprazole over the potential therapeutic dose range （ 20 - 60mg）. METHODS In a randomized three - way crossover study, twelve healthy subjects were took single intravenous drip doses of 20,40,60 mg of Rabeprazole. Following a washout period, all subjects received a single dose of 20 mg Rabeprazole administrated orally. Plasma concentrations were determined at selected time intervals for 10 h（ or 12 h）hours. The pharmacokinetic parameters were calculated by DAS software. RESULTS The elimination half- life of Rabeprazole after iv injection of 20,40,60 mg Rabeprazole was about 1 -2 h, C, naxincreased linearly from 0. 9628 ± 0. 1321 μg. mL- 1 to 2. 9782 ± 0. 4947 μg. mL- 1 with the increasing dose. Moreover, the area under the plasma concentration with time curve increased linearly within the dose range of 20 - 60 mg （AUC0-t from 1. 3247 ± 0. 3597 μg. h. mL- 1 to 3. 9924 ± 1.0111 μg. h. mL- 1, AUC0-∞ from 1. 3390 ± 0.3706 μg. h. mL- 1 to 4. 0410 ± 1. 0355 μg. h. mL-1 ）. In oral administration, tmax WaS 3. 4 ± 0. 8 h, t1/2 was 1.38 ±0.50 h, Cmax WaS 0. 5078 ± 0. 1798 μg. mL- 1, AUCo-twas 1.0518 ± 0. 4606 μg- h. mL- 1 ,A UC0-∞ was 1. 0641 ± 0. 4756 μg. h. mL -1
,respectively. CONCLUSION Rabeprazole exhibited a linear pharmacokinetic profile at the doses in the range of 20 - 60 mg. Dose - dependent parameters （ C AUC） increased in an approximately dose - proportional manner from 20 mg to 60 mg. There were no significant differences in the different dose groups. Differences in the pharmacokinetic parameters between genders were not statistically significant, but differences in t1/2 of 20 mg were statistically significant.
出处
《华西药学杂志》
CAS
CSCD
北大核心
2014年第2期176-179,共4页
West China Journal of Pharmaceutical Sciences
基金
十二五重大新药创制科技重大专项资助项目(批准号:2012ZX09303015)
辽宁省科学技术计划项目(项目编号:2009225020)
