Pharmacokinetic drug interaction between epirubicin and interferon-alpha-2b in serum and red blood cells.
The influence of interferon-alpha-2b (CAS 99210-65-8, IFN) on the pharmacokinetics of epirubicin (CAS 56420-45-2, EPR) was investigated in 10 patients (4 male, 6 female). EPR was injected as an i.v. bolus over 2 min in a dose of 60 mg/m2 IFN was pre-administered 3 times a week in a dose of 5 x 10(6) IU as a s.c. injection. The comparison of the pharmacokinetics after injection of EPR and EPR+IFN did not show remarkable differences. A statistical significant influence in regard to the terminal elimination half-life (gamma-HL) and the total clearance (CLtot) was found, indicating a reduction of gamma-HL from 18.18 +/- 16.7 for EPR to 8.47 +/- 8.67 h for EPR+IFN and a reduction of the total clearance from 72.33 +/- 55.4 ml/min for EPR to 48.41 +/- 12.7 ml/min for EPR+IFN. The area under the concentration-time curve (AUC, according to the 3-compartment model) increases under the influence of IFN from 2004 +/- 1105 ng/ml.h for EPR up to 2582 +/- 1024 ng/ml.h for EPR+IFN. However, this increase is statistically irrelevant due to the high deviation ranges. Besides, the influence of IFN on the interactions of EPR with red blood cells (RBCs) was investigated in 6 patients under the above conditions. The percental concentration of EPR in RBCs is reduced from 35.4% to 34.7% after administration of IFN. Two metabolites, 13-dihydroepirubicin (M I) and 7-deoxydoxorubicinone (M II), were detected both in serum and RBCs, whereas IFN showed no significant interference with the metabolism or with the binding of the metabolites to RBCs.
Bandak
S
S
Institute of Pharmaceutical Chemistry, University of Vienna, Austria.
Czejka
M
M
Schüller
J
J
Schernhammer
E
E
D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D004347:Drug Interactions; D015251:Epirubicin / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015251:Epirubicin