Pharmacokinetics of epirubicin after intravenous administration: experimental and clinical aspects.
A method is described for the extraction and determination of epirubicin and its main metabolites epirubicinol and glucuronides in plasma, using high performance liquid chromatography (HPLC) with fluorescence detection. The extraction was performed with column Sep-Pak C18, which allowed a quantitative recovery of compounds. This method was used first in studies performed in five rabbits after intravenous administration of 3 mg/kg epirubicin, and later in a cancer patient, who received 50 mg/m2 epirubicin in rapid intravenous infusion. Although not statistically significant, kinetics of epirubicin were fitted in both cases to a tri-exponential model. Common metabolites were detected in rabbits and human, particularly the glucuronides. However, kinetics of epirubicin glucuronides and epirubicinol glucuronides were very different. Production and elimination were very fast in rabbit at very low levels and were undetectable two hours after administration, while in human, elimination was slower and greater amounts were detected 1-2 h after administration. The rabbit seemed to be an interesting animal species for pharmacokinetic studies because of easy blood sampling, detection of small amounts of glucuronides and because of a good fit to tri-exponential kinetics model.
Dine
T
T
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté de Pharmacie, Lille, France.
Luyckx
M
M
Brunet
C
C
Cazin
M
M
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015251:Epirubicin / Q000097:blood / Q000493:pharmacokinetics*; D005965:Glucuronates / Q000097:blood; D006801:Humans; D007275:Injections, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011817:Rabbits
D005965:Glucuronates; D015251:Epirubicin