Pharmacokinetics and metabolism of epirubicin during repetitive courses of administration in Hodgkin's patients.
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/m2) or escalated from 25 to 35 and 50 mg/m2. 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.
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000378:metabolism* / Q000627:therapeutic use; D001711:Biotransformation; D004317:Doxorubicin / Q000378:metabolism* / Q000627:therapeutic use; D015251:Epirubicin; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D006207:Half-Life; D006689:Hodgkin Disease / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D005965:Glucuronates; D015251:Epirubicin; D004317:Doxorubicin