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Abstract
1. The absorption, distribution, metabolism and excretion of 2-[3′-(2″-quinolyl-methoxy)phenylamino]benzoic acid (QMPB), a novel leukotriene D4/E4 antagonist, were investigated in rat, dog, guinea pig and man.
2. The oral absorption of the potassium salt of QMPB was rapid and almost complete (90%) in rats, and about 50% in dogs. In man, high oral bioavailability was indicated. Absorption in dogs of the zwitterion form was only 7%.
3. The distribution of 3H-QMPB was examined in rats and guinea pigs. Whole-body autoradiography in rats showed that radioactivity was concentrated predominantly in the liver, bile and intestinal lumen, after both oral and i.v. administration.
4. A major metabolite was identified as the O-ester β-glucuronide of QMPB.
5. Renal excretion in rat, dog and man was very low. In rat, almost complete biliary excretion of QMPB as the glucuronide conjugate was demonstrated.
6. Pronounced enterohepatic circulation of QMPB was demonstrated in rats, and the plasma concentration curves and the negligible renal excretion in dog and man also indicate enterohepatic circulation in these species.