Distribution of 1-aminobenzotriazole in male rats after administration of an oral dose

Abstract

1. ¹⁴C-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 concentration of total radioactivity in various tissues and organs measured.

2. The compound appears to be absorbed slowly with 50% of the radioactivity remaining in the stomach at 6 h after dosing and maximum plasma and tissue concentrations were observed at 24 h.

3. Approximately 71% of the dose of ¹⁴C was excreted in the urine and 12% in the faeces over 72 h, indicating oral absorption of at least 71%. Tissue-to-plasma ratios of ¹⁴C were highest in the liver, adrenals and kidneys, which all contain significant amounts of cytochrome P450; the half-lives of elimination for total ¹⁴C in liver, adrenals and kidneys were ∼24, 16 and 12 h, respectively, while the half-life in plasma was ∼9h.

4. ABT was metabolized by N-acetylation, with the acetylated product attaining concentrations equal to ABT in the plasma; two other major metabolites were also excreted in the urine namely, the N-glucuronide of 1-aminobenzotriazole and the N-glucuronide of benzotriazole.