COMPARISON OF THE EFFECTIVENESS OF EICOSAPENTAENOIC ACID ADMINISTEREDAS EITHER THE FREE ACID OR ETHYL-ESTER AS AN ANTICACHECTIC AND ANTITUMOR AGENT

A comparison has been made of the effectiveness of eicosapentaenoic (E PA) acid administered as either the free acid or the ethyl ester as an anticachectic and antitumour agent in mice bearing an experimental ca chexia-inducing tumour (MAC16 colon adenocarcinoma). While the free ac id of EPA was effective in reversing host body weight loss and inhibit ing tumour growth the ethyl ester was ineffective in either respect at the same dose level, even when administered with a high fat diet. The lack of effectiveness of the ethyl ester correlated with the inabilit y to reach effective plasma and tumour concentrations of EPA over the initial time period. Whereas effective plasma concentrations of EPA we re achieved within 24 h after administration of the free acid, a time lapse of 96 h was required with the ethyl ester, even when combined wi th a high fat diet. Due to the acuteness of the MAC16 model this time is too long for a therapeutic benefit to be realized.