PHARMACOLOGIC STUDIES OF FLUMETHIAZIDE (ADEMOL)

¹ Squibb Institute for Medical Research, New Brunswick, New Jersey

In mice, the intravenous LD50 ± S.E. of flumethiazide was 910 ± 10 mg/kg. No deaths were observed after the oral administration of 8 g/kg.

In an in vitro comparison with acetazolamide, flumethiazide exhibited relatively little inhibition of carbonic anhydrase.

After intravenous administration to normal dogs, flumethiazide (1) had negligible effects on hemodynamic and autonomic functions, (2) was eliminated by the kidneys primarily by tubular secretion, (3) markedly increased the urinary excretions of sodium and chloride, enhanced to a lesser degree the voidance of potassium, and (4) had little effect on the excretion of bicarbonate. Flumethiazide thus appeared to be a more specific saluretic agent than chlorothiazide.

After intravenous administration to one acidotic and to one alkalotic dog, flumethiazide effectively promoted the urinary excretions of sodium and chloride but did not alter the respective electrolytic imbalances.

After oral administration to normal dogs, flumethiazide (1) was rapidly absorbed from the gastrointestinal tract, (2) was maximally effective with respect to natriuresis at a dose of about 10 mg/kg, (3) produced no acid-base imbalance in large chronic doses, and (4) demonstrated lasting effectiveness as a saluretic agent.