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 hepatocell ular carcinoma (HCC) has become increasingly popular. However, investi gations to determine the extent to which the Lipiodol sequesters the a nthracycline in the liver have been limited. Concern has been expresse d that such emulsions are not stable and that the anthracycline is, th erefore, released rapidly into the circulation. We studied the pharmac okinetics of epirubicin (50 mg m(-2)) in five patients with nonresecta ble primary hepatocellular carcinoma after infusion of an epirubicin/l ipiodol emulsion via the hepatic artery. We used a reliable and specif ic high-performance liquid chromatography assay that allows quantitati on of plasma concentrations of epirubicin, epirubicinol, epirubicin gl ucuronide, and epirubicin aglycone. Although a large interpatient vari ability 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 dr ug in the liver. It would appear that more stable formulations of epir ubicin/Lipiodol are required to increase the efficacy of this form of treatment. We suggest that pharmacokinetic studies should accompany cl inical evaluation of emulsions of epirubicin/Lipiodol for the treatmen t of HCC.