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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 |
| TITLE： | |
| 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 |
| 阅读数： | 512 次 |
| 本月下载数： | 7 次 |
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