PT  - JOURNAL ARTICLE
AU  - C S Godin
AU  - P A Crooks
TI  - N-methylation as a toxication route for xenobiotics. II. In vivo formation of N,N'-dimethyl-4,4'-bipyridyl ion (paraquat) from 4,4'-bipyridyl in the guinea pig.
DP  - 1989 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 180--185
VI  - 17
IP  - 2
4099  - http://dmd.aspetjournals.org/content/17/2/180.short
4100  - http://dmd.aspetjournals.org/content/17/2/180.full
SO  - Drug Metab Dispos1989 Mar 01; 17
AB  - The biotransformation of 4-phenylpyridine and 4,4'-bipyridyl to N-methylated quaternary ammonium metabolites in guinea pig and rabbit has been examined. Neither animal species excreted the neurotoxin N-methyl-4-phenylpyridinium ion as a urinary metabolite after ip administration of 4-phenylpyridine. However, treatment of rabbits with 4,4'-bipyridyl resulted in the formation of N-methyl-4,4'-bipyridinium ion in the urine (1.2% of the administered dose), and ip administration of 4,4'-bipyridyl to guinea pigs afforded both N-methyl-4,4'-bipyridinium ion and N,N'-dimethyl-4,4'-bipyridinium ion (paraquat) as urinary metabolites (0.8% and 2.9%, respectively, of the administered dose). The detection of the lung toxin paraquat as a urinary metabolite of 4,4'-bipyridyl is a significant finding, in that it represents the first documented report of the formation of a toxic metabolite via the N-methylation pathway.