Rectal absorption and distribution of Diflucortolone valerate and Lidocaine in hemorrhoid model rats

Abstract

Intrarectal application of drugs has been used as an effective administration route, howsver, the absorption and distribution of drugs may be changed in pathological state of the rectum, especially in the case of hemorrhoid disease. Rectal absorption and distribution of ³H-diflucortolone valerate (³H-DFV), which is an anti-inflammatory steroid, and ¹⁴C-lidocaine (¹⁴C-LDC) in hemmorrhoid model rats were compared with that in normal rats.
The hemmorrhoid model rats, were prepared by means of application of croton oil into rectum of rats, showed high vascular permeability and edema.
³H-DFV and ¹⁴C-LDC were applied into the rectum as a suppository of combination of both drugs at the dose of 0.01mg/kg of ³H-DFV and 2mg/kg of ¹⁴C-LDC, and the anus was sealed by glue for 3h. Rectal absorption of ³H -DFV was slow and low, while that of ¹⁴C-LDC was faster than ³H-DFV. The profile and pharmacokinetic parameters (C_max, T_max and AUC) of blood kinetics of both radioactivities in the hemmorrhoid model rats were not different statistically from that observed in intact rats. These results indicate that the kinetics of rectal absorption of both drugs can't be changed by hemorrhoid disease. The radioactivity in the rectum, target tissue of anti-hemorrhoid drug, showed 100 folds higher value of that in the blood, and no difference in the radioactivities in the rectum was observed between intact and hemorroid rats. The autoradiogram revealed the uniform distribution of the radioactivities in the hemorrhoid rectum.
These results indicate that the rectal application is more effective therapy than the systemic one, and the kinetics after rectal application shows no diffe rence between intact and hemorrhoid model rats.