Absorption Behavior of Orally Administered Drugs in Rats Treated with Propantheline

The effect of gastrointestinal (GI) transit rate on the absorption behavior of orally administered drugs was investigated using rats pretreated with propantheline. The propantheline-treatment reduced the transit rate in all segments to approximately 50%. The absorption behavior was examined for thre...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 1998-09, Vol.87 (9), p.1081-1085
Main Authors: Haruta, Shunji, Iwasaki, Norio, Ogawara, Ken-ichi, Higaki, Kazutaka, Kimura, Toshikiro
Format: Article
Language:English
Subjects:
Ampicillin - pharmacokinetics
Animals
Anti-Bacterial Agents - pharmacokinetics
Area Under Curve
Biological and medical sciences
Bronchodilator Agents - pharmacokinetics
Cephalexin - pharmacokinetics
Digestive system
Gastrointestinal Motility - drug effects
Gastrointestinal Motility - physiology
Intestinal Absorption - drug effects
Male
Medical sciences
Models, Biological
Muscarinic Antagonists - pharmacology
Pharmacology. Drug treatments
Propantheline - pharmacology
Rats
Rats, Wistar
Theophylline - pharmacokinetics
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Summary:The effect of gastrointestinal (GI) transit rate on the absorption behavior of orally administered drugs was investigated using rats pretreated with propantheline. The propantheline-treatment reduced the transit rate in all segments to approximately 50%. The absorption behavior was examined for three model drugs with different absorption characteristics: theophylline as a highly absorbable drug without the first-pass elimination, ampicillin as a poorly absorbable one, and cephalexin as a highly absorbable one via carrier-mediated transport system. In the GI transit-retarded state, the Tmax of the plasma concentration-time curve was delayed in all the three drugs. However, the extent of bioavailability was not changed in theophylline and cephalexin. On the other hand, the extent of bioavailability of ampicillin was increased in rats pretreated with propantheline. This might be caused by the increased residence time in the absorption site, i.e., small intestine. These results were generally predicted by use of the convolution method based on the GI-Transit-Absorption Model, which was developed in our previous study, using the GI transit rate parameters in rats pretreated with propantheline. The analysis using this model could clarify that the substantial absorption site of cephalexin moved to the upper region of the small intestine by the reduction of the GI transit rate.
ISSN:0022-3549
1520-6017
DOI:10.1021/js980117+