Effect of calcium inhibitors and calcium mobilizers on doxorubicin accumulation in rat myocardial tissue.

The effect of four calcium-modulating agents on myocardial doxorubicin (DXR) accumulation was studied: the calcium-inhibitors verapamil (0.1 microM), trifluoperazine (5 microM) and flunarizine (0.05 microM) and the calcium-mobilizer taurine (50 mM). Myocardial cells of isolated Langendorff rat hearts receiving the drugs showed a significantly enhanced 14C-DXR uptake. These observations are in contrast with the hypothesis that DXR accumulation processes may be related to a decrease in calcium influx and suggest that a combined therapy with DXR and calcium-modulating agents might enhance the drug-induced cardiotoxicity.