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  

Pharmacokinetic study of granisetron hydrochloride transdermal patch by multiple administrations in beagle dogs

作　　者：陈姗姗[1] 孙莹莹[1] 韦阳[1] 王恪申[1] CHEN Shan-shan SUN Yin-yin WEI Yang WANG Ke-shen(Institue of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China)

机构地区：[1]浙江省医学科学院,药物研究所,杭州310013

出　　处：《中国比较医学杂志》2017年第2期44-48,共5页Chinese Journal of Comparative Medicine

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)

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。Objective To establish an HPLC-MS/MS method for determination of the plasma concentration of granisetron hydrochloride administered by transdermal patch in Beagle dogs and evaluate its pharmacokinetics. Methods Six beagle dogs were given topically applied transdermal patches（ 72 h） for 6 times with an interval of 24 h. HPLC-MS/MS was applied to determine the concentration of granisetron hydrochloride in blood samples,thereafter the pharmacokinetic parameters were calculated. Results The trough concentration of Cmin was 0. 0459 ng/m L and 0. 2593 ng/m L after the first-dosage and sixth-dosage of granisetron transdermal patches,respectively. The peak concentration of Cmax was 0. 4637 ng/m L and 0. 4637 ng/m L,respectively. The AUC0 ~ 96 was 18. 92 h·ng/m L and 40. 21 h·ng/m L,respectively. The Tmax was 48. 3 hours and 45. 3 hours,respectively,and the MRT0-96 was 48. 9 hours and 45. 84 hours,respectively.Conclusions The concentration of granisetron has accumulation effect after repeated administration of granisetron hydrochloride transdermal patches,and it reaches a steady state on the sixteenth day by multiple administrations.

关 键 词：盐酸格拉司琼透皮贴剂 BEAGLE犬 HPLC-MS/MS 药代动力学 

分 类 号：R-33[医药卫生]