Metabolism of epirubicin to glucuronides: relationship to the pharmacodynamics of the drug.

In pharmacokinetic studies of epirubicin, we observed that its main metabolite, epirubicin glucuronide, presented a marked interpatient variation. It was even possible to separate the patients into two groups: those with a high epirubicin glucuronide:epirubicin plasma ratio and those with a low ratio, with few patients in between. We retrospectively analyzed the clinical files of 48 patients who had been subjected to a pharmacokinetic study of epirubicin. We observed that those with a low epirubicin glucuronide:epirubicin ratio had significantly lower plasma levels of fibrinogen and alpha 2-globulins, suggesting that a reduced glucuronidation of epirubicin could be associated with hepatocellular insufficiency. These patients also had significantly lower percentages of change in granulocytes after therapy and responded better to the course of treatment studied. We cannot presently propose a hypothesis to explain these observations.