Rat jugular vein catheterization model for the cross-over pharmacokinetic study of midazolam new formulation / 国际药学研究杂志

ABSTRACT

Objective To establish and optimize the rat jugular vein catheterization model in our lab, and perform a cross-over study using this model to compare the pharmacokinetic characters of a newly developed midazolam formulation to the existing preparation. Methods Six SD rats (half male and half female) received the right jugular vein catheterization when the rats were sufficiently anesthetized. One week after the operation, all the rats were used to conduct a cross-over double period pharmacokinetic study. Totally1.33 mg/kg midazolam solutions from automatic needle and clinic available injection were adminisered to the jugular vein catheterization rats via im route. The washout period was 5 days. Exact volume of blood samples at designed time points were taken through the catheter. After preparation, the concentrations of midazolam in rat plasma were determined by using established LC-MS/MS method. The corresponding pharmacokinetic parameters were calculated by WinNolin software. Results The rat jugular vein catheterization model was successfully built. Blood was easily sampled and rats were well tolerated, meeting the requirement of repeated blooding. This model solved the bottleneck of cross-over study performed in rats. The pharmacokinetic behavior of newly developed midazolam formulation had no difference with that of clinic injections. The relative bioavailability was around 99%. Conclusion Rat jugular vein catheterization model is proved to be that of a propagating technique to do the cross-over study and to evaluate the pharmacokinetic characters of novel formulations.