ABSORPTION AND 1ST-PASS-EFFECT OF SALBUTA MOL AFTER INTRADUODENAL ANDINTRARECTAL ADMINISTRATION IN RABBITS

To understand the previous result of higher bioavailability of rectal salbutamol (SB) compared with oral SB, in situ experiments using rabbi t duodenal and rectal loop were carried out. After the intravenous (i. v.) and intraportal (i.p.) dosing of SB, fraction of dose which avoids the hepatic first-pass-effect (Fh) was calculated from the areas unde r the blood concentration-time curve (AUC). The Fh was about 10% and u nchanged significantly with increasing i.p. dose (5-20 mg). Intraduode nal (i.d.) or intrarectal (i.r.) dosing of SB was made after the i.v. and i.p. dosing, and the AUC's and the residual amount in the loop wer e obtained to estimate the parameters. The results of the i.d. and i.r . dosing were as follows; for the extent of bioavailability (EBA), 7.7 +/-1.5% and 14.5+/-2.3%, for the fraction of dose absorbed (fa), 93.9/-3.7% and 33.8+/-3.3%, and for the fraction of absorbed SB which avoi ds first-pass-effects (F), 8.4+/-1.9% and 43.0+/-6.0% (mean+/-S. E., n =4). Consequently, SB dosed i.d. was absorbed completely, and received first-pass-metabolism in the mucosa (about 20%) and then in the liver (about 90%), which caused the low bioavailability. While, in i.r. dos ing, SB absorption was poor. However, higher bioavailability was obtai ned owing to about 40% of rectal venous blood flow which bypasses the liver and negligible first-pass-metabolism in the mucosa (about 4%).