DISTRIBUTION OF 1-AMINOBENZOTRIAZOLE IN MALE-RATS AFTER ADMINISTRATION OF AN ORAL DOSE

1. C-14-labelled 1-aminobenzotriazole (ABT), a suicide inactivator of cytochrome P450, was synthesized and administered orally to male rats. The rats were killed at 1, 6, 24, 48 or 72 h after dosing and the con centration of total radioactivity in various tissues and organs measur ed. 2. The compound appears to be absorbed slowly with 50% of the radi oactivity remaining in the stomach at 6 h after dosing and maximum pla sma and tissue concentrations were observed at 24 h. 3. Approximately 71% of the dose of C-14 was excreted in the urine and 12% in the faece s over 72 h, indicating oral absorption of at least 71%. Tissue-to-pla sma ratios of C-14 were highest in the liver, adrenals and kidneys, wh ich all contain significant amounts of cytochrome P450; the half-lives of elimination for total C-14 in liver, adrenals and kidneys were app roximately 24, 16 and 12 h, respectively, while the half-life in plasm a was approximately 9 h. 4. ABT was metabolized by N-acetylation, with the acetylated product attaining concentrations equal to ABT in the p lasma; two other major metabolites were also excreted in the urine nam ely, the N-glucuronide of 1-aminobenzotriazole and the N-glucuronide o f benzotriazole.