Pharmacokinetic and Pharmacodynamic Evaluation of Crebanine Patch in Rats

  OBJECTIVE  To compare the pharmacokinetic differences between the percutaneous and intragastric administration of Crebanine in rats. To evaluate the effect of Crebanine patch on anti-arrhythmia in rats and the mechanism of Crebanine on calcium channel.

  METHODS  The plasma concentration of Crebanine in rats was determined by HPLC. The anti-arrhythmic effect of Crebanine transdermal administration was observed in the model of barium chloride induced arrhythmia in rats, and Whole Cell recording was used to detect the effect of Crebanine on calcium channel current.

  RESULTS  The main pharmacokinetic parameters of Crebanine patch for transdermal administration (400 mg·kg^-1) were as follows: AUC_0-∞=(204.500±170.496)mg·h·L^-1; T_max=(10.333±0.745)h; C_max=(1.968±0.147)mg·L^-1 (n=6). The main pharmacokinetic parameters of Crebanine solution for intragastric administration (40 mg·kg^-1) were as follows: AUC_0-∞=(26.980±6.672)mg·h·L^-1; T_max=(0.086±0.024)h; C_max=(8.991±2.343)mg·L^-1 (n=6). Compared with the negative group, the time required for recovery of sinus rhythm was significantly shortened (P < 0.01), and the number of rats recovering sinus rhythm significantly increased (P < 0.01) after transdermal administration of the patches in 79, 158, 316 mg·kg^-1 groups. The number of rats that could recover sinus rhythm within 20 min after administration increased significantly (P < 0.001). The number of rats that maintained sinus rhythm for more than 20 min after the restoration increased significantly (P < 0.01). Both T-type and L-type calcium channels were inhibited by Crebanine.

  CONCLUSION  The administration of Crebanine patch has slow elimination and sustained release effect, can significantly inhibit barium chloride induced arrhythmia in rats by inhibiting calcium channels, and significantly prolong the action time, so as to achieve the purpose of reducing toxicity and increasing efficiency.