Epirubicin

Epirubicin

DRUG NAME: Epirubicin
SYNONYM(S): 4’-epidoxorubicin,1 IMI-28,1 NSC-2569421 COMMON TRADE NAME(S): PHARMORUBICIN®,2 ELLENCE®3 CLASSIFICATION: anthracycline antineoplastic antibiotic4 MECHANISM OF ACTION:
2 The mechanism of action of epirubicin appears to be related to its ability to bind to nucleic acids. It forms a complex 4 with DNA by intercalation between base pairs, resulting in inhibition of DNA and RNA synthesis. Intercalation also 3,4 triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Binding to cell membranes and plasma 2 proteins may also be involved. Epirubicin also generates cytotoxic free radicals.3,4 Epirubicin is the 4’-epimer of 4 DOXOrubicin; i.e., there is a different spatial orientation of the hydroxyl group at the 4’ carbon of the sugar moiety. This difference may account for faster elimination and reduced toxicity.2

PHARMACOKINETICS:
Distribution rapidly and widely distributed into tissues3; may concentrate in red blood cells, whole blood 3 concentrations are approximately twice those of plasma cross blood brain barrier? no 3 volume of distribution 21-27 L/kg plasma protein binding3 77% extensive hepatic metabolism; also metabolized by other organs and cells, including red blood cells3 active metabolite(s) epirubicinol (13-OH epirubicin)3; cytotoxic activity onetenth that of epirubicin; plasma levels consistently lower than epirubicin inactive metabolite(s) glucuronides of epirubicin and epirubicinol; DOXOrubicin; aglycones of doxorubicinol, 73 deoxydoxorubicin, and 7-deoxydoxorubicinol predominantly hepatobiliary; rapid elimination of parent compound from plasma urine 9-10% within 48 h2; 20-27% within 4 days3 feces 40% of dose recovered in bile within 72 h terminal half life3 33 h 3 65-83 L/h clearance 3 no differences observed clearance may be decreased in elderly women3
3

Metabolism

Excretion

Gender Elderly

Adapted from standard reference unless specified otherwise.

BC Cancer Agency

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