Pharmacokinetics and metabolism of epirubicin during repetitive courses of administration in Hodgkin's patients

Abstract

We studied the pharmacokinetics and metabolism of epirubicin ( 4′-epidoxorubicin) in ten patients suffering from Hodgkin's disease and receiving three successive injections of epirubicin at 15-day intervals in a combined chemotherapy regimen. Doses were either constant ( 35 mg/m 2 ) or escalated from 25 to 35 and 50 mg/m 2 . Epirubicin metabolism was characterized by the presence of high levels of epirubicin glucuronide in plasma and urine. The area under the time-concentration plasma curve of epirubicin glucuronide reached almost that of unchanged epirubicin (mean ratio = 0.7–0.85), whereas the cumulative urinary excretion of epirubicin glucuronide was one-half of that of epirubicin (mean ratio = 0.45–0.51). Repeating or escalating the doses did not change the levels of the glucuronide significantly. Only a trend towards higher relative levels of glucuronide could be noticed at the lowest dose. The pharmacokinetic parameters of epirubicin were characterized by a high total plasma clearance (mean value: 70–85 1/hr) and a mean elimination half-life of 25–35 hr. Repeating or escalating the doses was followed by a slight increase of the total plasma clearance in most patients, without changes of the elimination half-life. The cumulative urinary excretion was 11–12% of the dose administered and did not vary significantly as a function of time or dose.