Mechanism of the cardioprotective effects of docetaxel pre-administration against adriamycin-induced cardiotoxicity

We revealed that pre-treatment with docetaxel (doc) 12 h before adriamycin (adr) administration significantly reduced adr-induced toxic death compared with the simultaneous dosing schedule that was commonly used in previous studies. we considered that pre-treatment with doc relieves adr-induced cardiotoxicity. in this study,we investigated the influence of doc on the pharmacokinetics and pharmacodynamics of adr in order to clarify the mechanism by which doc pre-treatment relieves adr-induced cardiotoxicity. when adr and/or doc was intravenously administered,the doc pre-treatment (doc-adr) group showed significantly less toxic death than the adr-alone group. we examined hepatopathy,nephropathy,leukopenia,and cardiotoxicity,all of which can cause toxic death. of these toxicities,adr-induced cardiotoxicity was significantly relieved in the doc-adr group. to elucidate the mechanism by which doc pre-treatment relieved adr-induced cardiotoxicity,lipid peroxidation as a proxy for the free radical level and the pharmacokinetics of adr were measured. there was no difference in the pharmacokinetics of adr between the adr and doc-adr groups. on the other hand,the doc-adr group showed significantly inhibited lipid peroxidation in the heart compared with the adr group. it was considered that doc pre-administration inhibited adr-induced free radicals and decreased cardiotoxicity. © the japanese pharmacological society.