Oral idarubicin--an anthracycline derivative with unique properties

Idarubicin belongs to a group of anthracyclines in which the methoxyl group in position 4 of the D ring in the aglycone moiety is replaced by a hydrogen atom. Lipophilicity is increased compared with other anthracyclines; as a result, idarubicin is the first anthracycline that can be administered orally while at the same time retaining its antitumor activity. In addition, the lipophilicity enables the transition of the substance, especially of the metabolite, to the cerebrospinal fluid. The metabolite idarubicinol is formed in high concentrations; this is particularly true with oral administration. Compared with all other anthracyclines, it has a very long half-life. It is the first anthracycline metabolite to have the same cytotoxic activity as the parent compound. The cardiotoxicity of idarubicin, being lower than that of other anthracyclines at equally effective doses, is even more reduced with oral administration. Preclinical and clinical experiences with oral idarubicin are reviewed.