盐酸小檗碱对大鼠体内他克莫司药动学的影响
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篇名: 盐酸小檗碱对大鼠体内他克莫司药动学的影响
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摘要: 目的:研究盐酸小檗碱单次、多次给药对大鼠体内他克莫司药动学的影响,为两者联合用药提供参考。方法:将30只大鼠随机分为5组,每组6只,第1组大鼠单次灌胃他克莫司;第2组大鼠每日灌胃他克莫司2次,连续给药1周;第3组大鼠先单次灌胃盐酸小檗碱,5 min后单次灌胃他克莫司;第4组大鼠先每日灌胃他克莫司2次,连续给药1周,第8天时先灌胃盐酸小檗碱5 min后再灌胃他克莫司1次;第5组大鼠每日灌胃盐酸小檗碱2次,每次间隔5 min后相应灌胃他克莫司1次,连续给药8 d。盐酸小檗碱给药剂量均为200 mg/kg,他克莫司给药剂量均为0.945 mg/kg。末次灌胃他克莫司后0、5、15、30 min和1、2、3、4、6、8、12 h,分别从各组大鼠的眼眶后静脉丛取血约0.3 mL,采用液相色谱-串联质谱法(LC-MS/MS)测定大鼠全血中他克莫司的浓度,应用DAS 2.0软件进行药动学研究。结果:与第1组比较,第3组大鼠体内的他克莫司药动学参数AUC0-12 h、AUC0-∞和MRT0-12 h显著降低(P<0.05),第4组大鼠体内他克莫司所有药动学参数差异均无统计学意义(P>0.05);与第2组比较,第4组大鼠体内他克莫司药动学参数AUC0-12 h显著降低、CLz显著升高(P<0.05),第5组大鼠体内他克莫司所有药动学参数差异均无统计学意义(P>0.05)。结论:单次、多次灌胃盐酸小檗碱均对大鼠体内他克莫司的药动学有影响,表现在血药浓度有下降的趋势,需谨慎联用。
ABSTRACT: OBJECTIVE: To study the effects of berberine hydrochloride on the pharmacokinetics of tacrolimus in rats after single or multiple administration, and to provide reference for clinical combination therapy. METHODS: 30 rats were randomly divided into 5 groups, with 6 rats in each group: group one was treated with single administration of tacrolimus; group two was treated with tacrolimus intragastrically, twice a day, for consecutive 1 week; group three was treated with single administration of berberine hydrochloride, 5 min later given single administration of tacrolimus; group four was treated with tacrolimus intragastrically, twice a day, for consecutive 1 week, and then given tacrolimus intragastrically once 5 min after intragastric administration of berberine hydrochloride on the 8th day; group five was treated with berberine hydrochloride intragastrically, twice a day, and given tacrolimus intragastrically every 5 min, for consecutive 8 d. The doses of berberine hydrochloride and tacrolimus were 200 mg/kg and 0.945 mg/kg. The blood samples 0.3 mL were collected from posterior orbital venous plexus of rats 0, 5, 15, 30 min and 1, 2, 3, 4, 6, 8, 12 h after last intragastric administration of tacrolimus. The concentration of tacrolimus in rat whole blood was determined by LC-MS/MS. DAS 2.0 software was used for pharmacokinetic study. RESULTS: Compared with group one, the pharmacokinetic parameters AUC0-12 h, AUC0-∞ and MRT0-12 h of tacrolimus in rats were decreased significantly in group three (P<0.05),while there was no statistical significance in all pharmacokinetic parameters of tacrolimus in group four (P>0.05). Compared with group two, AUC0-12 h of tacrolimus was decreased significantly while CLz was increased significantly in group four (P<0.05); there was no statistical significance in all pharmacokinetic parameters of tacrolimus in group five (P>0.05). CONCLUSIONS: Single and multiple intragastric administration of berberine hydrochloride has a certain effect on the pharmacokinetics of tacrolimus in rats, it shows that there is a downward trend in blood drug concentration and needs to be used with caution.
期刊: 2019年第30卷第5期
作者: 杨远霞,钟克波,潘兴,赵宏寰,王黎青
AUTHORS: YANG Yuanxia,ZHONG Kebo,PAN Xing,ZHAO Honghuan,WANG Liqing
关键字: 盐酸小檗碱;他克莫司;药动学;单次给药;多次给药;大鼠
KEYWORDS: Berberine hydrochloride; Tacrolimus; Pharmacokinetics; Single administration; Multiple administration; Rats
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