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 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.
Haruta
S
S
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
Iwasaki
N
N
Ogawara
K
K
Higaki
K
K
Kimura
T
T
D000667:Ampicillin / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000493:pharmacokinetics*; D002506:Cephalexin / Q000493:pharmacokinetics*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008954:Models, Biological; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011413:Propantheline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D011413:Propantheline; D000667:Ampicillin; D013806:Theophylline; D002506:Cephalexin