Reduced uptake of liposomal idarubicin in the perfused rat heart

Although idarubicin is one of the most important anthracyclines and liposomal formulations seemed less cardiotoxic than free drug formulations, there are no definite data on cardiac uptake of liposomal encapsulated idarubicin. This study has been designed to determine uptake and negative inotropic action of liposomal idarubicin in the single-pass isolated perfused rat heart. Idarubicin-bearing liposomes, composed of 1,2-distearoyl-sn-glicero-phosphocholine, 1,2-distearoyl-sn-glicero-phosphoethanolamine-N-[poly(ethylene glycol)2000], and cholesterol were administered as a 10-min constant infusion of 1 mg followed by a 70-min washout period. Outflow concentration and left ventricular-developed pressure were measured and compared with data of free idarubicin observed previously under the same experimental conditions. Liposomal encapsulation significantly reduced cardiac uptake of idarubicin to about 15% and extensively diminished its negative inotropic action to less than 5% of the values observed for free idarubicin.