Intestinal first-pass metabolism of N-nitrosodibutylamine in vascularly autoperfused jejunal and ileal loops of rats

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Abstract
N-Nitrosodi-[1-14C] butylamine (NDBA) has been shown to undergo a high first-pass metabolism in isolated perfused rat small intestinal segments. Metabolites resulting from ω-hydroxylation of NDBA, the bladder carcinogens N-nltroso-butyl-(4-hydroxybutyl)amlne (NB4HBA) and N-nltroso-butyl-(3-carboxypropyl)-amine (NB3CPA), accounted for >90% of the total radioactivity absorbed. In the present study using vascularly perfused rat small intestinal segments, the high first-pass metabolism of NDBA could be confirmed under nearin vivo conditions despite the much higher absorption rate. At the end of the 36 min experimental period 70–80% of the dose have been absorbed via the portal blood as opposed to 1–10% of the dose after 2 h in vitro perfusion. ω-Hydroxylation was again the most important metabolic pathway. However, the relationship of NB3CPA to NB4HBA was shifted in favor of NB4HBA, indicating a concentration and absorption rate dependency in the further metabolism of NB4HBA to NB3CPA.

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