Age-related changes in the pharmacodynamics of verapamil

Age-related differences in the pharmacodynamics of numerous drugs are well documented. In this study, changes in the pharmacodynamics of verapamil were examined in anesthetized and unanesthetized puppies (6 weeks old) and adult dogs. Unanesthetized puppies and adult dogs were given verapamil (0.5 mg/kg intravenously and 2.5 mg/kg orally), and anesthetized dogs received only intravenous infusions. Plasma samples and ECG tracings were taken over a 4- to 7-hour period. Plasma verapamil was determined by high-pressure liquid chromatography with spectrofluorometric detection. Puppies exhibited a shorter t1/2 than adults after intravenous administration (62.3 +/- 10.8 minutes compared to 87.3 +/- 7.8 minutes). Puppies had a greater area under concentration (AUC) after oral dosing than adults, indicating a greater amount of the dose reaching the systemic circulation. The PR interval was significantly prolonged in adults but not in puppies, even though the blood levels in the puppies were greater than those in the adults. Therefore, even though there is little variation in the pharmacokinetic parameters between adult dogs and puppies, there is a marked reduction in the sensitivity of the puppies to the ECG effects of verapamil.