Distribution of 1-aminobenzotriazole in male rats after administration of an oral dose.
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 approximately 24, 16 and 12 h, respectively, while the half-life in plasma was approximately 9 h. 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.
Town
C
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Department of Drug Metabolism, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Henderson
L
L
Chang
D
D
Mortillo
M
M
Garland
W
W
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D008297:Male; D051381:Rats; D014018:Tissue Distribution; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
D014230:Triazoles; C033020:1-aminobenzotriazole