家兎十二指腸内及び直腸内投与時のサルブタモールの吸収と初回通過効果

概要

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To understand the previous result of higher bioavailability of rectal salbutamol (SB) compared with oral SB, in situ experiments using rabbit 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 under the blood concentration-time curve (AUC). The Fh was about 10% and unchanged significantly with increasing i.p. dose (5-20 mg). Intraduodenal (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 were 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 avoids 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. dosing, SB absorption was poor. However, higher bioavailability was obtained owing to about 40% of rectal venous blood flow which bypasses the liver and negligible first-pass-metabolism in the mucosa (about 4%).
公益社団法人日本薬学会の論文
1993-10-25