The effects of disopyramide phosphate on serum glucose and glucose counterregulation in the dog.
The effect of oral administration of the antiarrhythmic disopyramide phosphate (DPP) on serum glucose and glucose counterregulation was determined in beagle dogs. In addition, the hypoglycemic effect of DPP, a racemate, and its optical isomers was determined. DPP produced dose-dependent significant decreases in serum glucose concentrations. Maximum decreases in serum glucose concentrations were approximately 10% at 10 mg/kg, 15% at 30 mg/kg, and 30% at 100 mg/kg when DPP was given as single doses, and 30% at 100 mg/kg when DPP was given as three divided doses. In each case, serum glucose concentrations returned to control values within 24 to 30 hr. To evaluate the effect of DPP on glucose counterregulation the recovery from acute insulin-induced hypoglycemia was determined. No differences of any practical significance were observed between the insulin tolerance curves of control and 50-, and 100-mg/kg DPP groups. Thus, the overall glucose counterregulatory response following insulin challenge was unaffected by DPP. The hypoglycemic effects of DPP, (S)-(+)-DPP, and (R)-(-)-DPP were compared by examining the ratio of the areas under the curve of serum glucose concentration to serum drug concentration. The absolute ratio for the (S)-(+) isomer was significantly greater than that of the (R)-(-) isomer, indicating that the hypoglycemic effect of DPP is largely due to its (S)-(+) isomer.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004206:Disopyramide / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D013237:Stereoisomerism; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D004206:Disopyramide