2-Naphthol metabolism and metabolite transport in the isolated guinea pig mucosa: further evidence for compartmentation of intestinal drug metabolism.
As an extension of a previous study on the metabolism of 14C-1-naphthol (1-N) by the isolated guinea pig mucosa (Sund & Lauterbach 1986), the isomeric compound 2-naphthol (2-N, 50-130 nmol/ml) has now been examined. 14C-Labelled drug was added to the luminal or contraluminal fluid bathing the two sides of jejunal or colonic mucosal sheets in a symmetrical set up. After aerobic incubation for 45 min. at 37 degrees, the fluid compartments and the tissue were analysed for parent drug and metabolites. Like 1-N 2-N was transformed into its sulphate and glucuronide. In the jejunum, 2-N was more extensively sulphated than 1-N, whereas in the colon the metabolite profiles (sulphate:glucuronide ratio) of the two isomers were similar. Generally, the metabolism rate of 2-N, its metabolite profile and metabolite transport pattern (lumen: blood distribution ratio) as well as the tissue accumulation of parent drug and metabolites, depended on the side of drug administration and on the tissue studied. Thus, changing the drug administration had a pronounced impact on the jejunal metabolism and transport, but caused only minor effects in the colon. In summary, this study emphasizes that drug metabolism and metabolite transport differ in the small and large intestine. The data further support the hypothesis that jejunal drug metabolism takes place in two compartments, of which the most active one is accessible from the lumen side and the other from the blood side. The possibility that colonic drug metabolism may also involve compartmentation should be considered although the present study provided very little evidence for this.
Sund
R B
RB
Institute of Pharmacology and Toxicology, Ruhr-University of Bochum, Germany.
Lauterbach
F
F
D000818:Animals; D001692:Biological Transport; D003106:Colon / Q000378:metabolism; D006168:Guinea Pigs; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D008297:Male; D009284:Naphthols / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D009284:Naphthols; D004364:Pharmaceutical Preparations; C029350:1-naphthol; C028405:2-naphthol