MULTIPLE-DOSE PHARMACOKINETICS OF EPIRUBICIN AT 4 DIFFERENT DOSE LEVELS - STUDIES IN PATIENTS WITH METASTATIC BREAST-CANCER

被引:36
作者
JAKOBSEN, P
STEINESS, E
BASTHOLT, L
DALMARK, M
LORENZEN, A
PETERSEN, D
GJEDDE, SB
SANDBERG, E
ROSE, C
NIELSEN, OS
MOURIDSEN, HT
JAKOBSEN, A
机构
[1] ODENSE UNIV HOSP,DEPT ONCOL,DK-5000 ODENSE,DENMARK
[2] RIGSHOSP,FINSEN INST,DEPT ONCOL,DK-2100 COPENHAGEN,DENMARK
[3] AARHUS UNIV HOSP,DEPT ONCOL,CLIN RES SECT,DK-8000 AARHUS,DENMARK
[4] ESBJERG CENT HOSP,DEPT ONCOL,ESBJERG,DENMARK
关键词
D O I
10.1007/BF00684959
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pharmacokinetic analysis of epirubicin and its metabolites epirubicinol and 7-deoxy-13-dihydro-epirubicinol aglycone during the first and the fourth courses of treatment was performed in 78 patients with metastatic breast cancer. The patients were treated every 3 weeks with epirubicin given as 10-min i.v. infusions at four different dose levels: 40, 60, 90 and 135 mg/m2. In most cases (76 of 78 cases), plasma concentration-time curves fitted to a three-compartmental pharmacokinetic model. The terminal half-life of epirubicin was independent of dose and duration of treatment. Large interindividual differences were demonstrated (mean t1/2-gamma, 21.6 +/- 7.9 h; range, 10.6-69 h; n = 110). In two subjects, extremely long half-lives and high serum bilirubin concentrations indicated impaired liver function. No correlation was found between the half-life and levels of liver alanine aminotransferase (ALAT) or serum creatinine. The metabolite epirubicinol appeared quickly after epirubicin administration and its half-lives were shorter than that of the parent compound (mean t1/2-gamma, 18.1 +/- 4.8 h; range, 8.2-38.4 h; n = 105). Formation of the aglycone metabolite was delayed and the half-life of this metabolite was shorter than that of epirubicin (mean t1/2-gamma, 13 +/- 4.6 h; range, 2.7-29 h; n = 104). The AUC of epirubicin and the total AUC (drug and metabolites) were linearly proportional to the dose, with the former value constituting two-thirds of the latter. A correlation was found between AUC and the plasma concentration of epirubicin at two time points (2 and 24 h after administration). The proposed model was AUC = 9.44 x c2 + 62.5 x c24 + 157.7 (r = 0.953).
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页码:63 / 68
页数:6
相关论文
共 19 条
[1]  
Akaike H., 1976, MATH SCI, V14, P5
[2]  
Ambrosini G, 1988, J CLIN ONCOL, V6, P976, DOI DOI 10.1200/JCO.1988.6.6.976
[3]  
BENJAMIN RS, 1974, CANCER, V33, P19, DOI 10.1002/1097-0142(197401)33:1<19::AID-CNCR2820330107>3.0.CO
[4]  
2-M
[5]  
BLACKSTEIN ME, 1987, P ECCO, V4, pA85
[6]  
CAMAGGI CM, 1985, DRUG EXP CLIN RES, V11, P285
[7]  
CAMAGGI CM, 1988, CANCER CHEMOTH PHARM, V21, P221
[8]  
CASSINELLI G, 1984, DRUG METAB DISPOS, V12, P506
[9]  
DEESEN PE, 1984, DRUG METAB DISPOS, V12, P6
[10]   COMPARATIVE PHARMACOKINETIC STUDY OF ADRIAMYCIN AND 4'EPI-ADRIAMYCIN AFTER THEIR SIMULTANEOUS INTRAVENOUS ADMINISTRATION [J].
EKSBORG, S ;
STENDAHL, U ;
LONROTH, U .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1986, 30 (05) :629-631