Verapamil disposition and cardiovascular effects in elderly patients after single intravenous and oral doses

Pharmacokinetics and pharmacodynamics of verapamil were studied in 11 elderly subjects (age = 79.67 +/- 4.74 years) and in 11 middle-aged subjects (age = 45 +/- 11.37 years) following intravenous (IV), single oral, and long-term oral administration. Plasma verapamil concentrations were determined using high-pressure liquid chromatography (HPLC). Twenty-four hour dynamic Holter electrocardiographic (ECG) recordings were employed to study heart rate (HR) and P-R interval. No difference in plasma half-life, distribution volume, body clearance, and area under the curve (AUC) was observed between the two groups after IV and oral verapamil administration. Blood pressure (BP) and HR were significantly reduced after verapamil IV administration in the elderly group only (p less than 0.05, p less than 0.01, respectively). After single and long-term oral administration, variable HR and BP responses were observed in both groups. The P-R prolongation following both IV and single oral doses exhibited a delay with respect to the peak plasma concentration, inducing a definite hysteresis loop. The slope of P-R variations (using a linear pharmacodynamic model) was greater in the elderly both after IV and single oral verapamil administration, but statistical significance was obtained only after the single oral dose (p less than 0.05). In the elderly group, after long-term oral administration, there was a significant prolongation of the P-R interval (p less than 0.0001) with respect to the corresponding time point of the 24-hour predrug period. Such variations in pharmacodynamic parameters in the elderly did not, however, cause any clinical problem.(ABSTRACT TRUNCATED AT 250 WORDS)