Accumulation of drugs by resting or beating cardiac tissue

The rate and degree of accumulation of 12 neutral, anionic and cationic drugs were studied in resting and 2 Hz-stimulated isolated left auricles of the guinea pig. The uptake process was accelerated in muscles driven electrically. The time needed to reach equilibrium was related to the extent of accumulation which in turn corresponded with the lipophilicity of the drug. The frequency-induced changes in the kinetics of the accumulation disappeared under reduced mechanical activity of the muscle. It is suggested that the increased mechanical activity enhances drug disposition within the extracellular space, so that more drug is available for transmembrane penetration.