The Effect of Food, Time of Dosing, and Body Position on the Pharmacokinetics and Pharmacodynamics of Verapamil and Norverapamil

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Abstract
To evaluate the influence of food, time of dosing, and body position on the steady‐state pharmacokinetics of an osmotically controlled formulation of verapamil (COER‐verapamil), each of 29 healthy men received one tablet a day at specified times in an open‐label, multiple‐dose, four‐period, crossover study. The verapamil tablets were administered in a randomized, balanced, crossover design: 240 mg at 8:00 AM on an empty stomach, subjects remaining ambulatory;240 mg at 8:00 AM on an empty stomach, subjects remaining supine for 8 hours; 240 mg at 10:00 PM with a standardized meal, subjects remaining supine for 8 hours; and 240 mg at 10:00 PM on an empty stomach, subjects remaining supine for 8 hours. Plasma verapamil concentrations were measured at steady state over the dosing interval. Steady‐state plasma concentrations were achieved by the fourth administration of the drug. Neither food nor posture had any effect on the pharmacokinetics of verapamil or norverapamil, or on hemodynamic measurements. Time of dosing did affect the rate of appearance and elimination of verapamil, but had no effect on the extent of verapamil absorption, norverapamil appearance, or hemodynamic measurements.