Pharmacokinetics of Verapamil and Hemodynamic Indices during Head-down Bed Rest

Abstract

The purpose of this work was to study the pharmacokinetics of the Ca ion antagonist verapamil (a single dose of 80 mg) and hemodynamics in nine volunteers with normal life activities (experiment 1) and on the second day of head-down (–8°) bed rest (experiment 2). The plasma concentration of verapamil was measured using high-performance liquid chromatography with fluorometric detection. Heart rate (HR), cardiac output (CO), stroke volume (SV) and general peripheral vascular resistance (GPVR) were measured using integral rheography according to Tishchenko (Mingograf-410, Russia); blood pressure (BP) was measured by Korotkoff sounds. Analysis of verapamil pharmacokinetics in both experiments showed identity of the averaged curve profiles that did not differ significantly. The pharmacokinetic parameters were comparable. Based on hemodynamics analysis, HR elevation 1 h after verapamil administration was the most common reaction in both experiments; a short CO rise and GPVR decrease were observed in experiment 2 1 h after administration. These hemodynamic shifts were not pathologic and did not deviate from the physiological range in healthy people; changes in verapamil pharmacokinetics were also not detected. These findings provide the grounds to recommend verapamil for rational pharmacotherapy of cardiovascular diseases that may develop in piloted space missions.