Influence of midazolam on pharmacokinetic parameters of procainamide in rabbits.

The majority of antiarrhythmic drugs have very narrow therapeutic range, and they may cause some side effects at doses used for curing cardiac arrhythmias. These drugs may enter different interactions. Procainamide also may interact with other drugs. Also some other drugs may change pharmacokinetics of procainamide, for example the iv anesthetics influence on pharmacokinetic parameters of procainamide. The aim of the study was to investigate the influence of midazolam on the plasma concentrations and pharmacokinetic parameters of procainamide in rabbits during two hours of observation. Procainamide was administered in rabbits at a dose of 13 mg/kg iv, and midazolam at 0.2 mg/kg iv. Procainamide levels were determined by immunofluorescence polarization method using ABBOTT reagents. Levels of procainamide were determined in the plasma at 5, 10, 15, 30, 45, 60, 90 and 120 min after the administration of procainamide. After administration of midazolam with procainamide, a decrease in plasma concentration of procainamide, together with its increased elimination, was observed.