The biological disposition of 1-methyl-3-keto-4-phenylquinuclidinium bromide in the rat and dog.

The biological disposition of 1-methyl-3-keto-phenylquinuclidinium bromide (MA540) has been studied in the rat and dog. Gastrointestinal absorption of the drug was considerably different in the 2 species; about 15% and 75% of the dose in the rat and dog, respectively. Tissue distribution after i.v. administration was characterized by generally high tissue/plasma drug ratios in the rat and by low plasma (the only tissue examined) levels in the dog. Drug localization was apparent in the liver and adrenals, and the highest average (24-h) concentration was found in those tissues. The distribution profile and the chemical nature of MA540 suggest that the compound was distributed, at least initially, in extracellular water. MA540 was not extensively metabolized by either species. Excretion, although initially fairly rapid, slowed such that whole body half-lives were estimated to be 21 h and 47 h in the rat and dog, respectively.