title: Disposition of epirubicin in an oily contrast medium after intravenous and intrahepato-arterial administration in liver cancer: a preliminary report.
abstract: The present study reports findings on the disposition of epirubicin after an intrahepato-arterial administration of the Lipiodol-drug complex, prepared by mixing the drug-aqueous phase with the iodized oil by ultra-sonification, in 14 patients with histologically proven hepatoma or hepatomegaly with serum alpha-fetoprotein level above 500 micrograms.l-1. The volume of Lipiodol used was 5 ml and the epirubicin dose was 50 mg.m-2. Blood samples were obtained at various time intervals up to 72 h post-dose. Serum concentrations of epirubicin were measured by liquid chromatography with fluorometric detection. The area under serum concentration-time curve (AUCinfinity0) was higher in the Lipiodol-epirubicin group (n = 8) while the clearance was faster and elimination t1/2 and mean residence time shorter in the plain epirubicin group (n = 3). However, interindividual variation in metabolism of epirubicin would affect serum level of the drug. In three patients who were given intravenous and intrahepato-arterial injections (90 mg.m-2) of plain epirubicin and Lipiodol-drug complex, the relative bioavailability of Lipiodol-epirubicin complex (F = 0.76 and 0.45) was lower than that of plain epirubicin (F = 0.80 and 0.73) in two patients while it was approximately 100% (F = 1.06 and 1.20) in one patient. It is likely that liver function of the patients might be modified by the disease state over a period of 3 months in the cross-over study. Further studies with larger patient samples are required to confirm if there is a targeting effect of the Lipiodol-drug complex toward hepatoma using a better formulation of the drug in Lipiodol.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T.
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: K
authors.initials: K
authors.lastname: Chan
authors.forename: W T
authors.initials: WT
authors.lastname: Leung
authors.forename: N W
authors.initials: NW
authors.lastname: Leung
authors.forename: S
authors.initials: S
authors.lastname: Ho
authors.forename: M
authors.initials: M
authors.lastname: Chan
authors.forename: C C
authors.initials: CC
authors.lastname: Lau
authors.forename: M
authors.initials: M
authors.lastname: Tao
authors.forename: W Y
authors.initials: WY
authors.lastname: Lau
authors.forename: W
authors.initials: W
authors.lastname: Shiu
mesh_terms: D000328:Adult; D000368:Aged; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics; D015251:Epirubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006499:Hepatic Artery; D006801:Humans; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007459:Iodized Oil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008113:Liver Neoplasms / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D003287:Contrast Media; D015251:Epirubicin; D007459:Iodized Oil