Disposition of epirubicin in an oily contrast medium after intravenous and intrahepato-arterial administration in liver cancer: a preliminary report.
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.
Lee
K
K
Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T.
Chan
K
K
Leung
W T
WT
Leung
N W
NW
Ho
S
S
Chan
M
M
Lau
C C
CC
Tao
M
M
Lau
W Y
WY
Shiu
W
W
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
D003287:Contrast Media; D015251:Epirubicin; D007459:Iodized Oil