[In vitro studies of intestinal absorption and biotransformation of furazolidone].
The intestinal biotransformation and absorption of the nitrofuran furazolidone were investigated in isolated gut cells and in the isolated perfused gut. In case of inhibiting furazolidone metabolism by high oxygen tension almost equal concentrations of the parent compound were measured on the mucosal and serosal side of the perfused gut segments. Lowering oxygen supply in order to adjust it to physiological conditions caused a complete degradation of furazolidone in isolated gut cells. Accordingly, hardly any unchanged furazolidone was detected on the serosal side of the isolated perfused gut. An open-chain cyanometabolite was formed in both systems indicating a reductive metabolic process which induces highly reactive intermediates. This metabolite also reached the serosal side of the gut representing the systemic circuit. Thus, the low systemic bioavailability is due to the considerable intestinal metabolism rather than a limited absorption. Unknown metabolites will reach the systemic circuit, the toxic potential of which is still obscure. Independent of its metabolic degradation, thus probably due to its redox cycle furazolidone inhibited intestinal functions as e. g. the flow of water and the transport of sodium.
Klee
S
S
Institut für Pharmakologie und Toxikologie, Fachbereich Veterinärmedizin, Freien Universität Berlin.
Ungemach
F R
FR
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D046508:Culture Techniques; D005664:Furazolidone / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats
D005664:Furazolidone
In-vitro-Untersuchungen zur intestinalen Resorption und Verstoffwechselung von Furazolidon.