In vitro absorption studies with carvedilol using a new model with porcine intestine called BM-RIMO (Boehringer-Mannheim ring model).
Carvedilol (CAS 72956-09-3, Dilatrend) is a beta-blocker with additional vasodilating, antiproliferative and antioxidative properties. It is indicated for the treatment of high tension (HT), coronary artery disease (CAD) and congestive heart failure (CHF). Carvedilol has been investigated in numerous in vivo studies and thus comparisons of in vitro results to in vivo observations are possible. In this publication the results of studies on the in vitro absorption of carvedilol in a new model called BM-RIMO (Boehringer-Mannheim ring model) using porcine intestine are reported. In particular the influence of absorption enhancers and of pH and the existence of absorption windows were examined and the relevance of the obtained data for in vivo conditions was estimated. The main route of carvedilol absorption seemed to be transcellular. In vitro as well as in vivo absorption decreased within the intestine in the following order: jejunum > ileum > colon. The highest amount of in vitro absorption of carvedilol was achieved in the jejunum at a neutral pH. Enhancers such as bile and the mucoadhesive agent chitosan had opposite effects on the absorption of the compound. The results indicate that BM-RIMO is a simple, cheap and fast tool for the investigation of the influence of absorption enhancers, pH and different parts of intestine on absorption. For carvedilol the in vitro model tends to overestimate absorption in the colon, possibly because of the lack of faeces.
Nolte
K
K
Pharmazeutisch-Chemisches Institut, Ruprecht-Karls-Universität, Heidelberg, Germany.
Backfisch
G
G
Neidlein
R
R
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000328:Adult; D000465:Algorithms; D000818:Animals; D001646:Bile / Q000378:metabolism; D002021:Buffers; D002227:Carbazoles / Q000493:pharmacokinetics*; D000077261:Carvedilol; D002686:Chitin / Q000031:analogs & derivatives / Q000494:pharmacology; D048271:Chitosan; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000493:pharmacokinetics*; D013552:Swine
D000319:Adrenergic beta-Antagonists; D002021:Buffers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D002686:Chitin; D048271:Chitosan