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Accumulation and metabolism of new anthracycline derivatives in the heart after IV injection into mice.

Abstract：

:In an attempt to establish a relationship between the pharmacokinetics in mouse heart of new anthracycline derivatives and their potential chronic cardiotoxicity and on this way to provide a useful and economical test for screening of new analogs, we followed the accumulation and metabolism of six anthracyclines in the mouse heart after single IV administrations of these drugs at equimolar doses. We found that the six drugs, i.e., daunorubicin (DNR), doxorubicin (DOX), rubidazone (RBZ), detorubicin (DET), N-L-leucyl-DNR (LEU-DNR) and N-L-leucyl-DOX (LEU-DOX), accumulate at various levels in the cardiac tissue and are metabolized to different extents, leading to the appearance in the heart of variable amounts of DNR or DOX. The total exposure of the mouse heart, as evaluated by calculation of the areas under the CXt curves, can be correlated qualitatively with the chronic cardiotoxicity of the six anthracyclines, as recently determined in the rabbit model. We therefore think that our study provides a simple, rapid, and inexpensive predictive test for the screening of new analogs for potential cardiotoxicity. Moreover, it offers the advantage of using the same species for determining the most favorable ratio between therapeutic activity and toxic side-effects.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Deprez-de Campeneere D,Baurain R,Trouet A

doi

10.1007/BF00255483

subject

Has Abstract

pub_date

1982-01-01 00:00:00

pages

193-7

issue

2

eissn

0344-5704

issn

1432-0843

journal_volume

8

pub_type

杂志文章

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