ABSTRACT:This study describes the pharmacokinetic parameters of gemopatrilat, a potent vasopeptidase inhibitor, in humans and the comparative biotransformation of the compound in rats, dogs, and humans after administration of a single oral dose of Approximately half of the drug-related radioactivity in 1-h plasma samples from rat, dog, and human was reduced chemically with dithiothreitol to gemopatrilat, suggesting that disulfide linkage occurred in all species. In addition, metabolites formed through S-methylation and amide hydrolysis were also detected in rat, dog, and human plasma. No gemopatrilat was detected in urine and fecal samples from all three species, indicating that the compound is extensively metabolized in vivo. The major metabolites identified in human urine and feces were also present in rat and dog. These data suggest that the metabolism of gemopatrilat in all three species were qualitatively very similar.
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