PHYSIOLOGICAL DISPOSITION AND METABOLISM OF 2-AMINOMETHYL-4-(1,1-DIMETHYLETHYL)-6-IODOPHENOL HYDROCHLORIDE

  • 1 January 1979
    • journal article
    • research article
    • Vol. 7  (5) , 330-334
Abstract
MK-447-14C [2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol hydrochloride], an antihypertensive diuretic, was well absorbed and metabolized in man, rats and dogs. Peak plasma levels of radioactivity was seen in these species 1-2 h 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 .apprx. 5% in rat and dog plasma. The half-life of the parent drug in human plasma was .apprx. 4 h. Human subjects excreted 96% of the dos, with 76% in the urine and 20% in the feces, in 3 days. Rats excreted 80% of an oral and 82% of an i.v. 2 mg/kg dose in 72 h, with 66% in the urine and 12-16% in the feces. In dogs given a 2 mg/kg dose i.v. the recovery of radioactivity in 72 h 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 .apprx. 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 3 species was in intact MK-447.