Pharmacologic effects of A-49816, a new high-ceiling diuretic.
The pharmacologic effects of A-49816, a high-ceiling, loop diuretic, were evaluated in a single-blind, placebo-controlled, randomized trial. Eighteen (18) normal volunteers aged 19 to 40 years were divided into three groups. The subjects in each group received either placebo or three increasing doses of A-49816 with at least a one-week washout between doses. Nine doses of A-49816 (0.5 to 20 mg) were administered during the entire study. Urine volume and excretion of electrolytes were measured at timed intervals following dosing. A-49816 increased urine volume and excretion of sodium and chloride. Significant saluresis, chloruresis and diuresis were seen in most time periods following administration of the highest doses (12.5, 15 and 20 mg) of A-49816. Kaluresis was not consistently seen at any dose. The mean rates of urine output and sodium and chloride excretion were increased relative to placebo within 2 hours of drug administration. The mean rates of urine formation and sodium and chloride excretion peaked at 2-4 hours and often remained elevated at the 6-12 hour interval.
Luther
R R
RR
Department of Clinical Research, Abbott Laboratories, Abbott Park, Illinois 60064.
Ringham
G L
GL
Steinberg
F J
FJ
Patterson
K J
KJ
Jordan
D C
DC
Rollins
D E
DE
Tolman
K G
KG
D000328:Adult; D001555:Benzene Derivatives; D002712:Chlorides / Q000652:urine; D002986:Clinical Trials as Topic; D004232:Diuretics; D006016:Glycolates / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011188:Potassium / Q000652:urine; D011897:Random Allocation; D012964:Sodium / Q000652:urine
D001555:Benzene Derivatives; D002712:Chlorides; D004232:Diuretics; D006016:Glycolates; C054819:ethyl (2,3-dichloro-4-(3-aminomethyl-4-hydroxybenzoyl)phenoxy)acetate; D012964:Sodium; D011188:Potassium