Anthracycline系抗悪性腫瘍剤adriamycin, 4'-epi adriamycinおよび4'-o-tetrahydropyranyl adriamycinの体内動態

抄録

Adriamycin (ADM), an anthracycline antibiotic, has shown marked activity against a wide range of human neoplasms, but its clinical use has been limited because of the risk of dose-dependent severe cardiotoxicity. The tissue distribution of ADM was studied by highperformance liquid chromatography in comparison to those of anthracycline analogues, 4'-o-tetrahydropyranyl adriamycin (THP) and 4'-epi adriamycin (4'-epi) synthesized to decrease the toxicity. The concentration of unmetabolized ADM in the heart was higher than those of THP and 4'-epi 24hr after administration; namely, the concentrations of THP and 4'-epi were one-fourth and one-fifth of that of ADM, respectively. The concentrations of the metabolized THP and 4'-epi (aglycones) showed low values 12hr after administration, being about one-fourth or one-eighth of that of ADM. The concentrations of these unmetabolized drugs in the liver and kidney were in the decreasing order of 4'-epi, ADM and THP and that of the aglycones was in the decreasing order of ADM, THP and 4'-epi. Because of the low affinity to heart tissue and low aglycone production, 4'-epi and THP were considered to be improved in the cardiotoxicity.