ETOPOSIDE PROTEIN-BINDING IN CANCER-PATIENTS

被引:6
作者
LIU, B
EARL, HM
POOLE, CJ
DUNN, J
KERR, DJ
机构
[1] UNIV BIRMINGHAM,QUEEN ELIZABETH HOSP,CANC RES CAMPAIGN,INST CANC STUDIES,TRIALS UNIT,BIRMINGHAM B15 2TH,W MIDLANDS,ENGLAND
[2] CITY HOSP,NHS TRUST,ST CHADS UNIT,BIRMINGHAM B18 7QH,W MIDLANDS,ENGLAND
关键词
ETOPOSIDE; PROTEIN BINDING; FREE FRACTION;
D O I
10.1007/BF00685801
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The protein binding of etoposide was studied in vivo in 36 cancer patients receiving etoposide therapy. Free etoposide was separated from plasma using an ultrafiltration method and the etoposide concentrations (free and total) were measured by high-performance liquid chromatography (HPLC). Considerable interpatient variation in the protein binding of etoposide was observed. The protein binding of etoposide varied from 80% to 97% (mean, 93%). Univariate analysis showed a significant inverse correlation between the free fraction of etoposide and serum albumin (r = -0.74), daily dose (r = -0.37) and age (r = -0.34). Multivariate analysis demonstrated that serum albumin and age were independent predictors of the etoposide free fraction. Serum bilirubin showed no correlation with etoposide protein binding, There is wide variation in etoposide protein binding in cancer patients, which is mostly dependent on serum albumin concentration.
引用
收藏
页码:506 / 512
页数:7
相关论文
共 24 条
[1]   COMPARISON OF HUMAN PHARMACOKINETICS OF VM-26 AND VP-16, 2 ANTINEOPLASTIC EPIPODOPHYLLOTOXIN GLUCOPYRANOSIDE DERIVATIVES [J].
ALLEN, LM ;
CREAVEN, PJ .
EUROPEAN JOURNAL OF CANCER, 1975, 11 (10) :697-707
[2]  
BRINDLEY CJ, 1985, CANCER CHEMOTH PHARM, V15, P66
[3]   PHARMACOKINETICS AND TOXICITY OF 2 MODALITIES OF ETOPOSIDE INFUSION IN METASTATIC NON-SMALL-CELL LUNG-CARCINOMA [J].
CHATELUT, E ;
CHEVREAU, C ;
BLANCY, E ;
LEQUELLEC, A ;
CANAL, P ;
ROCHE, H ;
HOUIN, G ;
BUGAT, R .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1990, 26 (05) :365-368
[4]  
CHEN GL, 1984, J BIOL CHEM, V259, P3560
[5]   THE CLINICAL-PHARMACOLOGY OF ETOPOSIDE AND TENIPOSIDE [J].
CLARK, PI ;
SLEVIN, ML .
CLINICAL PHARMACOKINETICS, 1987, 12 (04) :223-252
[6]   PREDICTION OF CREATININE CLEARANCE FROM SERUM CREATININE [J].
COCKCROFT, DW ;
GAULT, MH .
NEPHRON, 1976, 16 (01) :31-41
[7]  
DOMBERNOWSKY P, 1973, ACTA PATH MICRO IM A, VA 81, P715
[8]  
DONEHOWER RC, 1993, CANCER PRINCIPLES PR, P412
[9]   FACTORS AFFECTING INVITRO PROTEIN-BINDING OF ETOPOSIDE IN HUMANS [J].
FLEMING, RA ;
EVANS, WE ;
ARBUCK, SG ;
STEWART, CF .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1992, 81 (03) :259-264
[10]   CLINICAL-PHARMACOLOGY OF HIGH-DOSE ETOPOSIDE ASSOCIATED WITH CISPLATIN - PHARMACOKINETIC AND METABOLIC STUDIES [J].
GOUYETTE, A ;
DENIEL, A ;
PICO, JL ;
DROZ, JP ;
BAUME, D ;
OSTRONOFF, M ;
LEBAIL, N ;
HAYAT, M .
EUROPEAN JOURNAL OF CANCER & CLINICAL ONCOLOGY, 1987, 23 (11) :1627-1632