The diuretic response in normal volunteers to a new benzylamine, 2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol HCl.
A phase I dose-response study of 2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol HCl (MK-447) was performed with the following oral doses: 6.25, 12.5, 25, 50, and 100 mg. Each volunteer served as his own control. The study was carried out in double-blind fashion on a 5-Gm Na and K diet with a minimum 2000 ml fluid intake. Urine was fractionated and analyzed for sodium, chloride, potassium, calcium, uric acid, and volume. Comparisons (MK-447 minus control values) of the 24-hour total sodium, calcium, potassium, and volume excretion rates at 6.25, 25 and 100 mg MK-447 were as follows: sodium, 195, 345, and 528 muEq/min; chloride, 191, 365, and 756 muEq/min; potassium, 77, -3, and 65 muEq/min; and volumes, 1, 3.4 and 11.7 ml/min. MK-447 did not alter calcium excretion. Uric acid excretion was observed to decrease as the dose of MK-447 was increased, however, the serum uric acid level always remained within normal limits. MK-447 did not alter the physiologic parameters but did produce symptoms of volume contraction at 100 mg. Because no further dose increase was attempted, a plateau in the dose-response curve was not reached. Comparison of 100 mg MK-447 with 80 mg oral furosemide revealed similar potency and a somewhat longer duration of action for MK-447.
D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives; D002712:Chlorides / Q000652:urine; D004232:Diuretics; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D013997:Time Factors; D014527:Uric Acid / Q000652:urine
D002712:Chlorides; D004232:Diuretics; D010636:Phenols; D002084:Butylated Hydroxytoluene; D014527:Uric Acid; C013753:2-aminomethyl-4-t-butyl-6-iodophenol; D005665:Furosemide; D011188:Potassium