Epirubicin pharmacokinetics after intrahepatic arterial and intraperitoneal administration

• Published in: Drugs under experimental and clinical research Vol. 11; no. 4; p. 295
• Main Authors: Strocchi, E, Camaggi, C M, Rossi, A P, Angelelli, B, Comparsi, R, Franchini, A, Del Prete, P, Cola, B, Pannuti, F
• Format: Journal Article
• Language: English
• Published: Switzerland 1985
• Subjects: Adult; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Colonic Neoplasms - pathology; Doxorubicin - administration & dosage; Doxorubicin - metabolism; Epirubicin; Female; Hepatic Artery; Humans; Injections, Intra-Arterial; Injections, Intraperitoneal; Kinetics; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Liver Neoplasms - secondary; Male; Middle Aged; Rectal Neoplasms - pathology
• ISSN: 0378-6501

The high hepatic clearance of the new doxorubicin analogue epirubicin (4'-epidoxorubicin, epiDX) suggests a possible use of this drug in local and regional therapy where a first pass through the liver is required before the drug can reach systemic circulation. EpiDX pharmacokinetics was followed in advanced cancer patients with liver metastases or a primary tumour after single bolus administration in the hepatic artery, through a surgically implanted catheter and subcutaneous access port. The first-pass effect through the liver was appreciable and only a relatively low fraction of the drug reached systemic circulation. Mild leucopenia and alopecia were observed only in a patient with a hepatopulmonary shunt; this subject was actually exposed to higher epiDX plasma levels. Low intraperitoneal doses of epiDX were administered in a weekly schedule to advanced cancer patients with peritoneal metastases and ascites. Drug concentrations were monitored in the ascitic effusion and in plasma. A high concentration gradient was present between the peritoneal cavity and peripheral circulation. No relevant local or systemic toxicity was observed.