THE METABOLISM OF ICI 118,587, A PARTIAL AGONIST OF BETA-1-ADRENOCEPTORS, IN MICE, RATS, RABBITS, DOGS, AND HUMANS

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 12  (5) , 652-660
Abstract
The absorption, metabolism and excretion of 14C-labeled xamoterol (ICI 118,587) [a cardiac stimulant] were examined in mice, rats, rabbits, dogs and humans. There was incomplete absorption by all species after oral administration, ranging from 9% by humans to 36% by dogs. Most of the absorbed radioactivity was eliminated within 24 h of adminstration and the renal route predominated. Conjugates of the parent compound were the only observed metabolites in urine, the phenolic glucuronide being the principal animal metabolite and the phenol sulfate being the only human metabolite. There were marked interspecies variations in metabolite patterns and dogs were the only animal species in which the sulfate metabolite was detected. Comparison of the urinary metabolite patterns also showed higher output of the conjugates after oral administration than after i.v. administration, indicating that first pass metabolism was taking place. Little significant change in absorption or metabolism was seen over a range of oral doses; in rats, some saturation of the glucuronide-conjugating mechanism was observed but the sulfate-conjugating mechanism showed little, if any, diminished capacity at high dose levels in dogs. The use of fast atom bombardment mass spectroscopy for the determination of the MW of conjugates is described.

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