抄録
Carvedilol, a nonselective β-blocking agent, has been widely used in the treatment of hypertension, and angina pectoris. It is subject to an extensive hepatic first-pass metabolism following oral administration, with a reported systemic bioavailability of between 22 and 24%. Since it is commercially available only in tablet form, the rectum is an effective administration method for elderly patients and for whom it is difficult to swallow tablets. For this reason the rectal absorption of carvedilol was studied in rats.
The plasma carvedilol levels were found to be significantly higher than the oral administration levels at 15 min, 1, 4, 6, 8, 12 and 24 hr after the rectal administration of 20 mg/kg carvedilol. In addition, the drug pharmacokinetic parameters, comprising maximum plasma concentration (Cmax) was 1.7 times higher, and area under the concentration-time curve up to 24 hours (AUC0-24) was 2.2 times higher after rectal administration. In comparison to the AUC0-24 values, the relative bioavailability of carvedilol after oral administration was 19.3% and also after rectal administration was 42.2%.
These results are thought to be caused by a reduced first-pass metabolism, and the rectum was thus conformed to be an effective administration route for calvedilol.
