Biliary excretion and pharmacokinetics of 4'epidoxorubicin (epirubicin) in advanced cancer patients.
Plasma pharmacokinetics and biliary and urinary excretion of the new doxorubicin analogue, epirubicin, have been studied in three patients with extrahepatic obstruction and percutaneous biliary drainage. At variance with the reported observations concerning doxorubicin metabolism, conjugation of epirubicin and 13-dihydroepirubicin with glucuronic acid takes place, and corresponding amounts of 4'-o-beta-D-glucuronyl-4'-epidoxorubicin and 4'-o-beta-D-glucuronyl-13-dihydro-4'-epidoxorubicin can be found in the bile and urine. The total amount of unaltered drug and metabolites excreted in the bile in the first 4 days after treatment accounts for the 37%, 27%, and 40% of the administered dose; urinary excretion accounts for 19%, 16%, and 26%. Biliary clearance of epiDX (32.5, 8.1 and 21.6 l/h) is higher than renal clearance (15.2, 3.3 and 9.41 l/h). The relevance of the biliary disposition of epirubicin suggest prudent dose reduction in patients with impaired biliary drainage.
Camaggi
C M
CM
Strocchi
E
E
Comparsi
R
R
Testoni
F
F
Angelelli
B
B
Pannuti
F
F
D001646:Bile / Q000032:analysis*; D001682:Biological Availability; D002853:Chromatography, Liquid; D004317:Doxorubicin / Q000378:metabolism*; D015251:Epirubicin; D006801:Humans; D008107:Liver Diseases / Q000150:complications / Q000378:metabolism; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*
D015251:Epirubicin; D004317:Doxorubicin