TY - JOUR T1 - METABOLISM OF MYOSMINE IN WISTAR RATS JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1648 LP - 1656 DO - 10.1124/dmd.104.003087 VL - 33 IS - 11 AU - Wolfgang Zwickenpflug AU - Stefan Tyroller AU - Elmar Richter Y1 - 2005/11/01 UR - http://dmd.aspetjournals.org/content/33/11/1648.abstract N2 - The alkaloid myosmine is present not only in tobacco products but also in various foods. Myosmine is easily nitrosated, yielding 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) and the esophageal tobacco carcinogen N′-nitrosonornicotine. Due to its widespread occurrence, investigations on the metabolism and activation of myosmine are needed for risk assessment. Therefore, the metabolism of myosmine has been studied in Wistar rats treated with single oral doses of [pyridine-5-3H]myosmine at 0.001, 0.005, 0.5, and 50 μmol/kg body weight. Oral administration was achieved by feeding a labeled apple bite. Radioactivity was completely recovered in urine and feces within 48 h. At the two lower doses, 0.001 and 0.005 μmol/kg, a higher percentage of the radioactivity was excreted in urine (86.2 ± 4.9% and 88.9 ± 1.7%) as compared with the higher doses, 0.5 and 50 μmol/kg, where only 77.8 ± 7.3% and 75.4 ± 6.6% of the dose was found in urine. Within 24 h, urinary excretion of radioactivity was nearly complete with less than 4% of the total urinary output appearing between 24 and 48 h. The two major metabolites accounting for >70% of total radioactivity in urine were identified as 3-pyridylacetic acid (20–26%) and 4-oxo-4-(3-pyridyl)butyric acid (keto acid, 50–63%) using UV-diode array detection and gas chromatography-mass spectrometry measurements. 3-Pyridylmethanol (3–5%), 3′-hydroxymyosmine (2%) and HPB (1–3%) were detected as minor metabolites. 3′-Hydroxymyosmine is exclusively formed from myosmine and therefore might be used as a urinary biomarker for myosmine exposure in the future. The American Society for Pharmacology and Experimental Therapeutics ER -