RT Journal Article
SR Electronic
T1 The metabolic disposition of (S)-2-(3-tert-butylamino-2-hydroxypropoxy)-3-cyanopyridine in rats, dogs, and humans.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 163
OP 167
DO 10.1124/dmd.8.3.163
VO 8
IS 3
A1 S Vickers
A1 C A Duncan
A1 B H Arison
A1 R O Davies
A1 R Ferguson
A1 A G Zacchei
YR 1980
UL http://dmd.aspetjournals.org/content/8/3/163.abstract
AB Studies of the metabolic disposition of (S)-2-(3-tert-butylamino-2-hydroxypropoxy)-3-[14C]cyanopyridine (I) have been performed in humans, dogs, and spontaneously hypertensive rats. After an iv injection of I (5 mg/kg), a substantial fraction of the radioactivity was excreted in the feces of rats (32%) and dogs (31%). After oral administration of I (5 mg/kg) the urinary recoveries of radioactivity for rat and dog were 19% and 53%, respectively, and represented a minimum value for absorption because of biliary excretion of radioactivity. In man, bililary excretion of I appeared to be of minor significance because four male subjects, after receiving 6 mg of I p.o., excreted 76% and 9% of the dose of radioactivity in the urine and feces, respectively. Unchanged I represented 58% of the radioactivity excreted in human urine. The half-life for renal elimination of I was determined to be 4.0 +/- 0.9 /hr. In contrast, unchanged I represented 7% and 1% of excreted radioactivity in rat and dog urine, respectively. A metabolite of I common to man, dog, and rat was identified as 5-hydroxy-I, which represented approximately 5% of the excreted radioactivity in all species. Minor metabolites of I in which the pyridine nucleus had undergone additional hydroxylation were present in dog urine along with an oxyacetic acid metabolite, also bearing a hydroxylated pyridine nucleus.