Rats blood glucose by the GOD/POD method; serum insulin

Rats were injected with a freshly
prepared aqueous solution of alloxan monohydrate in two doses of 100 mg/kg and
50 mg/kg body weight intraperitoneally for two consecutive days. Fasting blood
sugar levels above 250 mg/dL were selected for the study.

Group I: disopyramide 3.6 mg/200g
body weight. Group II: metformin 2TD 18 mg/200g body weight. Group III:
disopyramide 3.6 mg/200 g body weight and then after 30 min, metformin 18
mg/200g body weight. Group IV: disopyramide for the 7 days with regular
feeding; later, after 18 h of fast, they were given the combined dose
(disopyramide + metformin) on the 8th day.

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A group of six rabbits was given
metformin 2TD 70 mg/1.5kg body weight, followed by a one week period of washout,
then the same group of rabbits was given disopyramide 14 mg/1.5kg body weight.
Later on washout period for one week, then same group was given disopyramide 14
mg/1.5kg, orally 30 mins prior to the administration of metformin (2TD) 70
mg/1.5kg body weight. Then, after the one week washout period, a similar group
of rabbits were given disopyramide 14mg/1.5kg body weight for 7 days
continuously; on the 8th day, disopyramide 14mg/1.5kg body weight was given
orally 30 mins prior to the administration of metformin (2TD) 70mg/1.5kg.

The blood samples were collected at
0, 1, 2, 3, 4, 6, 8, 10 and 12 h intervals from all the groups of rats after
drug administration and were subjected to estimation of blood glucose by the
GOD/POD method; serum insulin was estimated by radioimmunoassay; and the
insulin resistance index and ?-cell function were determined by homeostasis
model assessment.

The combination showed enhancement
the hypoglycemic activity. Metformin action was enhanced but may not be due to
the metabolic competitive inhibition exerted by disopyramide.

The disopyramide increased
pharmacodynamics of metformin after single and multiple dose administration in
rats and rabbits.

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