z-bo 2020-11-16 352

　　OBJECTIVE: To establish a blood concentration determination method for granisetron hydrochloride transdermal patch in Beagle dogs, and to reveal the pharmacokinetics of granisetron hydrochloride transdermal patch in Beagle dogs by multi-dose administration in Beagle dogs , To clarify its pharmacokinetic characteristics in Beagle dogs and provide important kinetic parameters.

　　Method: Beagle dogs were given granisetron hydrochloride transdermal patches 6 times, each patch lasted 72 hours, and the interval between each withdrawal and the next administration was 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.

　　Results: The trough concentration Cmin after the first dose and the sixth dose were 0.0459 ng/mL and 0.2593 ng/mL, the peak concentration Cmax were 0.4637 ng/mL and 1.3428 ng/mL, and the AUC0~96 were 18.92 h·ng/mL and 40.21 h·ng/mL, the Tmax after the first dose and the sixth dose were 48.3 h and 45.3 h, respectively, and MRT0-96 were 48.9 h and 45.84 h, respectively.

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