【Animal Modeling】-Pharmacokinetics Study of Granisetron Hydrochloride Transdermal Patch in Beagle Dogs with Multi-dose Administration

  Objective: To establish a method to determine the blood concentration of Beagle dog granisetron transdermal patch, to clarify the pharmacokinetic changes of Beagle dog granisetron transdermal patch after multiple administrations, and to provide a dynamic Features and important dynamic parameters.

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

  Results: After the first and sixth doses, the trough concentration Cmin was 0.0459g/mL and 0.25993g/mL, the peak concentration Cmax was 0.4637g/mL and 1.3428g/mL, AUC 0-96, g/mL 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: Multiple administrations of granisetron have a certain accumulation effect in the body, and it is stable after 16 days of multiple administrations.