Tocainide conjugation in humans: novel biotransformation pathway for a primary amine.
The metabolism of tocainide, an experimental antiarrhythmic drug, was studied in humans. Urinary excretion of unchanged drug was 28-55% in 24 hr after oral dosing. Urine hydrolysis with hydrochloric acid or beta-glucuronidase increased tocainide recovery to 55-79%. Saccharo-1,4-lactone inhibited the beta-glucuronidase-mediated tocainide recovery increase. Adjustment of urine to pH 13 produced a compound identified as 3-(2,6-xylyl)-5-methylhydantoin. Evidence suggests that it was derived from the same metabolite that formed the additional tocainide after acid or beta-glucuronidase treatment. Tocainide carbamoyl O-beta-D-glucuronide is the structure proposed for the metabolite. The suggested pathway for its formation involves the addition of carbon dioxide to the amino nitrogen of tocainide followed by uridine diphosphate-glucuronic acid conjugation.
D000813:Anilides / Q000378:metabolism* / Q000652:urine; D000889:Anti-Arrhythmia Agents / Q000378:metabolism* / Q000652:urine; D001711:Biotransformation; D002245:Carbon Dioxide / Q000378:metabolism; D005965:Glucuronates / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis
D000813:Anilides; D000889:Anti-Arrhythmia Agents; D005965:Glucuronates; D002245:Carbon Dioxide; D005966:Glucuronidase