Disposition of epirubicin after intraarterial administration in Lipiodol to patients with hepatocellular carcinoma.
Delivering emulsions of anthracycline drugs in Lipiodol, an iodinated poppy-seed oil, via the hepatic artery for the treatment of hepatocellular carcinoma (HCC) has become increasingly popular. However, investigations to determine the extent to which the Lipiodol sequesters the anthracycline in the liver have been limited. Concern has been expressed that such emulsions are not stable and that the anthracycline is, therefore, released rapidly into the circulation. We studied the pharmacokinetics of epirubicin (50 mg m-2) in five patients with nonresectable primary hepatocellular carcinoma after infusion of an epirubicin/Lipiodol emulsion via the hepatic artery. We used a reliable and specific high-performance liquid chromatography assay that allows quantitation of plasma concentrations of epirubicin, epirubicinol, epirubicin glucuronide, and epirubicin aglycone. Although a large interpatient variability in pharmacokinetics was observed, our results were similar to historical data after epirubicin intravenous therapy. Only the results from one patient provided evidence of significant retention of the drug in the liver. It would appear that more stable formulations of epirubicin/Lipiodol are required to increase the efficacy of this form of treatment. We suggest that pharmacokinetic studies should accompany clinical evaluation of emulsions of epirubicin/Lipiodol for the treatment of HCC.
Dodds
H M
HM
Department of Clinical Pharmacology, Princess Alexandra Hospital, Queensland, Australia.
Walpole
E T
ET
Rivory
L P
LP
Strong
R W
RW
Pond
S M
SM
D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D015251:Epirubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D007459:Iodized Oil / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D013535:Suspensions
D000903:Antibiotics, Antineoplastic; D013535:Suspensions; D015251:Epirubicin; D007459:Iodized Oil