RT Journal Article
SR Electronic
T1 Physiological disposition and metabolism of 2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol hydrochloride.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 330
OP 334
VO 7
IS 5
A1 D J Tocco
A1 F A deLuna
A1 A E Duncan
A1 R W Walker
A1 B H Arison
A1 W J Vandenheuvel
YR 1979
UL http://dmd.aspetjournals.org/content/7/5/330.abstract
AB MK-447-(14)C [2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol hydrochloride] was well absorbed and metabolized in man, rats, and dogs. Peak plasma levels of radioactivity were observed in these species 1-2 hr after oral administration of 2 mg/kg to rats and dogs and 25 mg to man. At the peak, parent drug represented about 15% of the radioactivity in human plasma and only approximately 5% in rat and dog plasma. The half-life of the parent drug in human plasma was approximately 4 h. Human subjects excreted 96% of the dose, with 76% in the urine and 20% in the feces, in 3 days. Rats excreted 80% of an oral and 82% of an intravenous 2-mg/kg dose in 72 hr, with 66% in the urine and 12-16% in the feces. In dogs given a 2-mg/kg dose intravenously, the recovery of radioactivity in 72 hr was approximately 99%, with 85% in the urine and 14% in the feces. The major metabolite in rat and dog urine, constituting approximately 90% of the urine radioactivity, was the O-sulfate conjugate of MK-447. In man, this metabolite accounted for 17% of the radioactivity in the urine. The major metabolite in human urine, constituting approximately 73% of the urine radioactivity, was tentatively identified as the N-glucuronide of MK-447. Less than 1% of the radioactivity in the urine of the three species was in intact MK-447.