EFFECTS OF THE CHRONIC ADMINISTRATION OF AMILORIDE HYDROCHLORIDE (N-AMIDINO-3,5-DIAMINO-6-CHLOROPYRAZINECARBOXAMIDE HYDROCHLORIDE DIHYDRATE) ON ELECTROLYTE BALANCE IN THE DOG

¹ Merck Institute for Therapeutic Research, West Point, Pennsylvania

Studies are described which show that 8 mg/kg/day doses of amiloride (N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride dihydrate) administered p.o. to dogs result in a retention of potassium with the development of hyperpotassemia. Studies were conducted to determine the effects of long-term administration of lower doses of amiloride on electrolyte balance. The drug was administered p.o. to young purebred beagle dogs, weighing from 7 to 17 kg, at doses of 2 and 4 mg/kg once daily for 78 to 80 days. Food intake, water intake and urinary and fecal output were measured. Food, urine, feces, selected tissues and serum were analyzed for various electrolytes. Determination of serum electrolytes demonstrated no significant dose- or time-related differences due to drug treatment. Electrolyte excretion expressed as total milliequivalenta excreted per three days, during drug weeks 1, 3, 11 and 12, revealed an increase in urinary sodium output with a concomitant decrease in fecal sodium excretion. Urinary potassium decreased whereas fecal potassium showed a dose-related increase. The correlation coefficients of the electrolyte outputs were consiatently higher at 4 mg/kg than at 2 mg/kg. Both drug-treated groups showed an inverse relationship between urinary and fecal electrolyte output, whereas the control group showed a highly significant direct relationship. The total output of potassium was decreased in a dose-related manner, whereas total sodium excretion remained unchanged. Tissue electrolytes (Na, K, Cl) were not altered. The usefulness of determining fecal in addition to urinary electrolyte excretion is also discussed.