THE EFFECT OF FOOD, TIME OF DOSING, AND BODY POSITION ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF VERAPAMIL AND NORVERAPAMIL

To evaluate the influence of food, time of dosing, and body position o n the steady-state pharmacokinetics of an osmotically controlled formu lation of verapamil (GOER-verapamil), each of 29 healthy men received one tablet a day at specified times in an open label, multiple-dose, f our-period, crossover study. The verapamil tablets were administered i n a randomized, balanced, crossover design: 240 mg at 8:00 AM on an em pty stomach, subjects remaining ambulatory; 240 mg at 8:00 AM on an em pty 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 ach ieved by the fourth administration of the drug. Neither food nor postu re had any effect on the pharmacokinetics of verapamil or norverapamil , or on hemodynamic measurements. Time of dosing did affect the rate o f appearance and elimination of verapamil, but had no effect on the ex tent of verapamil absorption, norverapamil appearance, or hemodynamic measurements.