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The Diuretic Response in Normal Volunteers To a New Benzylamine, 2‐Aminomethyl‐4‐(1,1‐dimethylethyl)‐6‐iodophenol HCI
Author(s) -
LOWENTHAL DAVID T.,
ONESTI GADDO,
AFFRIME MELTON B.,
SCHROGIE JOHN J.,
KIM KWAN E.,
BUSBY PATRICIA,
SWARTZ CHARLES D.
Publication year - 1978
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1978.tb02458.x
Subject(s) - clinical pharmacology , medicine , pharmacology , library science , computer science
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.