盐酸格拉司琼透皮贴剂在Beagle犬中多剂量给药的药代动力学研究

发布时间：2018-06-28 23:36

本文选题：盐酸格拉司琼透皮贴剂 + beagle犬　；参考：《中国比较医学杂志》2017年02期

【摘要】：目的建立盐酸格拉司琼透皮贴剂在Beagle犬中的血药浓度测定方法,通过Beagle犬多剂量给药,揭示盐酸格拉司琼透皮贴剂在Beagle犬体内的药代动力学变化规律,阐明其在Beagle犬体内的药代动力学特征,提供重要的动力学参数。方法 Beagle犬给予盐酸格拉司琼透皮贴剂6次,每次贴片持续72 h,每次撤药和下次给药间隔24 h。用建立的HPLC-MS/MS法测定血浆中的格拉司琼的浓度,根据所得的血浆药物浓度-时间曲线,计算药动学参数。结果第1次给药和第6次给药后的谷浓度Cmin分别0.0459 ng/m L和0.2593 ng/m L,峰浓度Cmax分别为0.4637 ng/m L和1.3428 ng/m L,AUC0~96分别为18.92 h·ng/m L和40.21 h·ng/m L,第1次给药和第6次给药后的Tmax分别为48.3 h和45.3 h,MRT0-96分别为48.9 h和45.84 h。结论多次给药后格拉司琼在体内存在一定的蓄积效应,并在多次给药后第16天到达稳态。
[Abstract]:Objective to establish a method for the determination of blood concentration of granisetron hydrochloride transdermal patch in Beagle dogs, and to reveal the pharmacokinetic changes of granisetron hydrochloride transdermal patch in Beagle dogs. To elucidate the pharmacokinetic characteristics in Beagle dogs and provide important kinetic parameters. Methods Beagle dogs were treated with granisetron hydrochloride transdermal patch for 6 times for 72 hours each time and the interval between withdrawal and the next administration was 24 hours. The concentration of granisetron in plasma was determined by HPLC-MS / MS method. The pharmacokinetic parameters were calculated according to the plasma concentration-time curve. Results after the first and sixth administration, the valley concentration of Cmin was 0.0459 ng/m / L and 0.2593 ng/m / L, respectively. The peak concentration C _ (max) was 0.4637 ng/m / L and 1.3428 ng/m / L respectively, and the peak concentration C _ (max) was 18.92 h / ng/m / L and 40.21 h / ng/m / L, respectively. The Tmax of the first and sixth dose was 48.3 ng/m / L, respectively. H and 45.3 h MRT 0-96 were 48.9 h and 45.84 h, respectively. Conclusion granisetron has a certain accumulative effect in vivo after multiple administration and reaches steady state on the 16th day after repeated administration.
【作者单位】：浙江省医学科学院药物研究所;
【基金】：浙江省科技厅培育创新载体项目(编号:2015F10032) 浙江省中医药科学研究基金项目(编号:2011ZA017)
【分类号】：R965

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