Pharmacology of verapamil. II. Impairment of glucose tolerance by verapamil in the conscious dog.

The effect of verapamil on glucose tolerance and insulin release in conscious, healthy dogs was studied at plasma drug concentrations which produce therapeutic cardiovascular effects. Plasma glucose and immunoreactive insulin were measured serially in each animal for 90 min after an intravenous glucose challenge (400 mg/kg), both during a control study and again during administration of verapamil. The drug was given by infusion protocols to produce plasma concentrations at low (84 +/- 9 ng/ml), intermediate (161 +/- 30 ng/ml), and high (367 +/- 51 ng/ml) ranges. Insulin release was impaired and glucose levels elevated at both the intermediate and the high verapamil concentrations, and to a similar degree. The reduction in insulin release and subsequent increase in plasma glucose is a pharmacologic effect of verapamil which occurs at drug concentrations likely to be achieved during clinical use.