[Mucus models for investigation of intestinal absorption mechanisms. 4. Comparison of mucus models with absorption models in vivo and in situ for prediction of intestinal drug absorption].
Intestinal absorption with an in vitro model using pig intestinal mucus was examined by means of in vivo and in situ experiments in the rat. With 10 compounds of different structure, in vitro, in situ, and in vivo models were tested. The in vitro model in the present form can only simulate the first step of intestinal absorption, namely diffusion through the mucus layer. Indeed, we found that one function of the intestinal mucus can be described being a molecular sieve with a molecular mass (MM) cut off within the range of about 600 to 700 [g/mol]. Absorption of substances with higher molecular mass remains at a low level. With the mucus model prediction of intestinal absorption of hydrophilic substances with MM < 600 to 700 [g/mol] will be possible, if the mass transport in the mucus layer is rate limiting. Independent of polarity, it is also valid for substances of MM > 600 to 700 [g/mol]. Estimation however, is not valid for lipophilic substances and MM < 600 to 700 [g/mol], when mass transport from the mucus to the adjacent compartments is rate limiting. Further optimization of the mucus model for a more extensive application seems possible and reasonable with respect to saving in vivo experiments with animals.
Matthes
I
I
Pharmazeutische Entwicklung, Sandoz Pharma AG, Basel, Schweiz.
Nimmerfall
F
F
Vonderscher
J
J
Sucker
H
H
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004058:Diffusion; D007408:Intestinal Absorption; D008297:Male; D008954:Models, Biological; D009093:Mucus / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
Muscusmodelle zur Untersuchung von intestinalen Absorptionsmechanismen. 4. Mitteilung: Vergleich des Mucusmodells mit Absorptionsmodellen in vivo and in situ zur Vorhersage intestinaler Wirkstoffabsorption.