Metabolism of tocainide in the rat

✍ Scribed by Raman Venkataramanan; Frank S. Abbott; James E. Axelson

• Book ID: 102406475
• Publisher: John Wiley and Sons
• Year: 1982
• Tongue: English
• Weight: 445 KB
• Volume: 71
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600710504

✦ Synopsis

The metabolism of tocainide, an oral antiarrhythmic agent, was studied in male Wistar rats following oral administration of 15 mg/kg of tocainide hydrochloride. Qualitative and quantitative identification of the metabolites in urine was carried out by GC-mass spectrometry and electron capture detector gas chromatography. About 1520% of the dose administered was excreted as intact drug in the urine. An additional 20% of the dose was present as acid hydrolysable conjugates. Enzymatic hydrolysis (P-glucuronidase) revealed half of the acid hydrolysable conjugates to be a glucuronide. The enzyme mediated hydrolysis was blocked by its specific inhibitor saccharo-1,4 lactone. N-acetyl tocainide, an oxidatively deaminated tocainide, an aldehyde adduct of tocainide, and a cyclic hydantoin derivative of tocainide were also identified as metabolites in the urine samples.

Keyphrases 0 Tocainide-oral antiarrhythmic agent, study of metabolism, rats Metabolism-of tocainide, after oral administration in rats 0 GC-mass spectrometry-determination of metabolism of tocainide, rats