格拉司琼鼻粉剂在比格犬体内的药动学及生物利用度研究

Study on pharmacokinetics and bioavailability of granisetron nasal powder in beagle

目的对格拉司琼鼻粉剂在比格犬体内的药动学进行研究,评价其生物利用度。方法比格犬采用随机、自身交叉给药,分别口服片剂、鼻腔给粉剂,用HPLC荧光方法测定格拉司琼血浆浓度。结果比格犬单剂量(2 mg)口服片剂、鼻腔给粉剂后的主要药动学参数tmax分别为(1.50±0.41)和(0.56±0.31)h,ρmax分别为(6.45±1.15)和(11.85±1.59)μg·L-1,AUC0-12分别为(25.14±3.75)和(34.53±2.97)μg·h·L-1,AUC0-∞分别为(28.46±4.17)和(38.22±2.84)μg·h·L-1,鼻粉剂对片剂的相对生物利用度为(139.02±17.49)%。结论格拉司琼鼻粉剂比片剂吸收快,生物利用度高。

OBJECTIVE To study the bioavailability of granisetmn nasal powder in beagle.METHODS A single dose of 2 mg granisetron tablet or nasal powder were given to beagles in a randomized crossover design. The plasma concentrations were determined by HPLC with fluorescence detection using bisoprolol fumarate as internal standard. RESULTS The pharmacokinetic parameters of granisetron tablet and nasal powder were as follows ： tmax （ 1.50 ± 0.41 ） and （ 0.56 ± 0.31 ） h, cmax （ 6.45 ± 1.15 ） and （ 11.85 ± 1.59 ） μg·L^-1,AUC0-12（25.14±3.75） and （34.53±2.97）μg·h·L^-1,AUC0-∞（28.46±4.17） and （38.22±2.84）μg·h·L^-1,respectively. The mean relative bioavailability of nasal powders vs tablets was （ 139.02 ± 17.49） %. CONCLUSION Granisetron nasal powder is rapidly abscrped and owns better bioavailability than the tablet.