[In vitro method for estimation of enteral absorption of clanobutin and other drugs].
Two models have been developed for the determination of in vitro absorption of 4-[4-chloro-N-(4-methoxyphenyl)-benzamidol]-butyric acid (clanobutin) and other agents. Permeability coefficients PM are obtained on artificial phospholipid collodion membranes which permit calculation of absorption coefficients k1 for anticipated human enteral absorption with consideration of physiological parameters. At a pH of 7--8 (small intestine) in particular, k1 shows good agreement with in vitro absorption determined in swine intestine and absorption constant ka derived from pharmacological studies in man. The kinetic absorption model simulates gastro-intestinal transport of the substance as well as local changes in pH. It allows calculation of anticipated human gastric (pH 3) and intestinal (pH 7.5) absorption rates with k1 for different gastric filling volumes. The calculated invasion curves are held against invasion curves calculated from pharmacokinetic studies in man. The comparison shows that all invasion curves calculated according to the kinetic absorption model for gastric filling volumes of 125--1000 ml are within the 95% confidence range; very good agreement exists above all with filling volumes of 125--250 ml. The prognostic value of permeation studies on artificial phospholipid collodion membranes and of the use of the kinetic absorption model in drug design is demonstrated by corresponding studies with chenodesoxycholic acid, indometacin, and clofibrinic acid.
D000042:Absorption; D000818:Animals; D001549:Benzamides; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003102:Colloids; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D007700:Kinetics; D008567:Membranes, Artificial; D008722:Methods; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010743:Phospholipids; D013552:Swine; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism
D001549:Benzamides; D003102:Colloids; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D010743:Phospholipids; D005680:gamma-Aminobutyric Acid
In-vitro-Methode zur Abschätzung der enteralen Absorption von Clanobutin und anderen Pharmaka.