MYOCARDIAL UPTAKE KINETICS OF TOCAINIDE ENANTIOMERS IN THE ISOLATED-PERFUSED RABBIT HEART

The extent of myocardial accumulation of tocainide, administered as si ngle enantiomers and as well as racemate, was determined in the isolat ed, spontaneous beating rabbit heart. The heart was retrogradely perfu sed at a constant rate and fractions of the perfusate were collected d uring and after infusion. Kinetic parameters for myocardial accumulati on and disposition of tocainide were indirectly determined from drug c oncentration/time course in the outflow perfusate. No stereoselectivit y in myocardial accumulation was observed. A two compartment model wit h mean half-lives for distribution and elimination of 0.60 and 3.78 mi n, respectively, was fitted to the accumulation and disposition data. At steady-state, tocainide enantiomers were accumulated about three ti mes in the myocardium relative to the perfusion liquid. (C) 1995 Wiley -Liss, Inc.