Pharmacologic effects of A-56234, a new high-ceiling diuretic.
The pharmacokinetic characteristics, the diuretic, saluretic, and uricosuric properties, and the safety of single, rising, oral doses of A-56234, a new high-ceiling diuretic, were evaluated in this double-blind, placebo-controlled, cross-over study. Each of three groups of eight subjects received placebo and three different single doses of the diuretic at 1-week intervals. Doses ranged from 0.5 to 80 mg. Significant, dose-related increases in urine volume and in urinary excretion of sodium and chloride were produced during the 24 hours after administration of 20, 40, 60, and 80 mg of the drug. Uricosuria was not observed at any dose. The drug was rapidly absorbed and displayed linear pharmacokinetics within the dose range studied. The elimination-phase plasma half-life was approximately 6 hours. Hepatic clearance was the main route of excretion in humans; only 2 to 10% of the parent drug was excreted in the urine. The drug was well tolerated and no clinically important adverse events were noted.
Luther
R R
RR
Department of Clinical Research, Abbott Laboratories, Abbott Park, IL 60064.
Ringham
G L
GL
Thomas
E W
EW
Patterson
K J
KJ
Tolman
K G
KG
D000293:Adolescent; D000328:Adult; D002712:Chlorides / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D012964:Sodium / Q000652:urine; D014528:Uricosuric Agents
D002712:Chlorides; D004232:Diuretics; D007555:Isoxazoles; D010080:Oxazoles; D014528:Uricosuric Agents; C058760:A 56234; D012964:Sodium