Separation and determination of liposomal and non-liposomal daunorubicin from the plasma of patients treated with Daunoxome.

Several liposomal formulations of anthracyclines have been developed recently and are currently used in the clinical setting. We describe a technique of separation and quantification of the liposomal and non-liposomal forms of daunorubicin in the plasma of patients treated with DaunoXome, a liposomal formulation of daunorubicin. The method we propose is based upon the property of liposomes to cross reversed-phase C18 silicagel cartridges without being retained, while non-liposomal drug is retained on the stationary phase and is eluted with methanol.

Preclinical evaluation of the cardiotoxicity of taxane-anthracycline combinations using the model of isolated perfused rat heart.

Paclitaxel strongly potentiates the cardiotoxicity of doxorubicin in the clinical setting. In this study, we aimed (1) to determine whether this potentiation could be reproduced in an ex vivo model and, if so, (2) to select drugs and protocols that did not cause this potentiation. The effect of paclitaxel and docetaxel on the cardiotoxicity induced by doxorubicin and epirubicin was studied using the model of isolated perfused rat heart.

Comparative cardiotoxicity of idarubicin and doxorubicin using the isolated perfused rat heart model.

Attempts to reduce the incidence of congestive heart failure following anthracycline therapy include the replacement of the parent compounds (especially doxorubicin) by less cardiotoxic analogs. Among these analogs, idarubicin (4-demethoxy-daunorubicin) was shown to be less cardiotoxic than doxorubicin in phase II clinical trials, but its actual cardiotoxicity has never been evaluated in large series and has never been compared to that of doxorubicin in relevant experimental models. Using the isolated perfused rat heart model, we compared the cardiac effects (developed pressure, contractility and relaxation of the left ventricle) induced by idarubicin to those induced by doxorubicin.

Development of the model of rat isolated perfused heart for the evaluation of anthracycline cardiotoxicity and its circumvention.

1. In order to develop a predictive model for the preclinical evaluation of anthracycline cardiotoxicity and the means of preventing it, we have studied the functional parameters of perfused hearts isolated from rats receiving repeated doses of several anthracyclines. 2.

Evaluation of anthracycline cardiotoxicity with the model of isolated, perfused rat heart: comparison of new analogues versus doxorubicin.

We have compared the cardiotoxicity of 3 anthracyclines in a model of isolated perfused rat heart using the Langendorff technique. The contractile state and ventricular compliance were studied. Doxorubicin, epirubicin and pirarubicin were perfused at concentrations of 10(-6) and 10(-5) M during 70 min.