Long-term toxicity of preoperative 4'-epidoxorubicin (Epi-adriamycin) in partially hepatectomized rats.
4'-Epidoxorubicin (Epi-A) administered immediately prior to liver resection has been suggested as treatment for patients with primary liver carcinoma. Long-term toxicity was studied in rats given a single dose of Epi-A intravenously immediately prior to a standard partial hepatectomy (PH). After 52 weeks only 9% of the rats given 5 mg/kg + PH were alive, 79% of the rats given 2 mg/kg + PH and 92% of the PH control survived. The weight gain of the rats given 5 mg/kg + PH was only 17% of that of PH controls. Signs of congestive heart failure were observed in some rats while in others moderate kidney lesions. No histopathological lesions were detected by light microscopy in heart, liver, spleen and bone marrow. For the rats given 2 mg/kg + PH body weight gain, microscopic observations and blood chemistry data (total protein, albumin, alkaline phosphatase, alanine aminotransferase, total bilirubin, creatinine and urea) were comparable to the PH controls. No significant differences in survival were registered between partially hepatectomized and sham-operated rats. The results indicate that Epi-A may be given preoperatively to liver resection without inducing long-term effects on vital organs.
Department of Clinical Pharmacology, Rikshospitalet, Oslo, Norway.
K S
KS
Hall
B
B
Lien
L
L
Mørkrid
O P
OP
Clausen
A
A
Bergan
H E
HE
Rugstad
D000818:Animals; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects*; D006498:Hepatectomy / Q000379:methods / Q000401:mortality; D008099:Liver / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011292:Premedication; D011300:Preoperative Care; D051381:Rats; D011915:Rats, Inbred BUF; D016019:Survival Analysis; D013997:Time Factors
D015251:Epirubicin