The influence of partial hepatectomy on the pharmacokinetics of preoperatively injected 4'-epidoxorubicin in rats.
Preoperative administration of 4'-epidoxorubicin (Epi-A) has been suggested as adjuvant therapy in patients undergoing liver resection for hepatocarcinoma. To assess the influence of partial hepatectomy on the pharmacokinetics of Epi-A, an experimental study in rats was undertaken in which 5 mg/kg Epi-A was given i.v. 10 min prior to a 2/3 hepatic resection or sham operation. Epi-A levels in liver tissue and plasma were determined using a sensitive and specific HPLC method. A marked uptake of Epi-A in liver tissue was found at 10 min after injection. The partially hepatectomized rats showed a 2-fold increase in AUC between 4 and 72 h as compared with the sham-operated controls. The terminal half-life from 24 to 72 h was not significantly changed by the partial hepatectomy. The plasma binding of Epi-A was measured at 4 h post-surgery. The fraction of unbound Epi-A was 0.16 in partially hepatectomized animals and 0.20 in sham-operated rats. The results indicate that when Epi-A is given prior to liver resection, a dose reduction might be necessary to avoid increased side effects due to the rise in AUC.
Hall
K S
KS
Department of Clinical Pharmacology, University of Oslo, Rikshospitalet, Norway.
Endresen
L
L
Schjerven
L
L
Rugstad
H E
HE
D000818:Animals; D001798:Blood Proteins / Q000032:analysis / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015251:Epirubicin / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D006207:Half-Life; D006498:Hepatectomy; D007275:Injections, Intravenous; D008099:Liver / Q000737:chemistry / Q000502:physiology*; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011915:Rats, Inbred BUF; D012107:Research Design; D013997:Time Factors
D001798:Blood Proteins; D015251:Epirubicin