动物实验 z-bo 2020-08-28 455

　　OBJECTIVE: To establish a method to determine the blood concentration of granisetron hydrochloride transdermal patch for beagle dogs, in order to clarify the pharmacokinetics of granisetron hydrochloride transdermal patch for beagle dogs and its effect in Beagle dogs. Pharmacokinetics in dogs. Characterize and provide important kinetic parameters.

　　Method: administer 6 doses of Granisetron hydrochloride transdermal patches to Beagle dogs, each patch lasts 72 hours, and the interval between each drug withdrawal and the next administration is 24 hours. The established HPLC-MS/MS method was used to determine the concentration of granisetron in plasma, and the pharmacokinetic parameters were calculated according to the obtained plasma drug concentration-time curve.

　　Result: After the first and sixth doses, the trough concentration Cmin were 0.0459g/mL and 0.25993g/mL, the peak concentration Cmax were 0.4637g/mL and 1.3428g/mL, respectively, and the AUC0?96 was 18.92 h? ng/mL and 40.21h? ng/mL, the Tmax after the first and sixth doses were 48.3h and 45.3h, respectively, and MRT0-96 were 48.9h and 45.84h, respectively.

　　Conclusion: Granisetron has a certain cumulative effect in the body after multiple doses, and reaches a steady state on the 16th day after multiple doses.