PT  - JOURNAL ARTICLE
AU  - D G Walker
AU  - M Hutchison
AU  - T A Shepard
AU  - P M Osborne
AU  - S M Allenby
AU  - A J Webb
AU  - N J Viney
AU  - M A Pue
AU  - R J Chenery
AU  - P J Wood
TI  - The disposition of 2-cyano-1-methyl 3-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)phenyl)guanidine in animals.
DP  - 1990 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 613--620
VI  - 18
IP  - 5
4099  - http://dmd.aspetjournals.org/content/18/5/613.short
4100  - http://dmd.aspetjournals.org/content/18/5/613.full
SO  - Drug Metab Dispos1990 Sep 01; 18
AB  - 2-Cyano-1-methyl 3-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)phenyl)guan idine (SK&F 94836), a new positive inotrope/vasodilator, is being evaluated for the treatment of congestive heart failure. The absorption, metabolism, and disposition of the compound have been investigated in the rat, mouse, and dog. SK&F 94836 was rapidly absorbed, widely distributed, and rapidly and completely excreted primarily via the urine. There was no evidence of metabolism of the compound in any of the species studied. The compound showed minimal interaction with cytochrome P-450. The compound contains a chiral center. The enantiomers have been shown not to interconvert in either rat or dog. The serum protein binding was low in all species, including humans, and exhibited no stereoselectivity. Studies conducted in rat and dog using constant rate co-infusion of racemic SK&F 94836 and radiolabeled inulin have demonstrated that SK&F 94836 is eliminated by active tubular secretion.