Altered protein binding of etoposide in patients with cancer.
Etoposide plasma protein binding (PB) is reported to be 94% based on in vitro studies using normal human serum albumin (SA). Etoposide PB in 17 patients with cancer receiving etoposide (50 to 100 mg/m2) and in plasma of 14 volunteers was determined by equilibrium dialysis with 3H-etoposide. The unbound fraction (Fu) in patients with cancer was 0.139 +/- 0.099 compared with 0.043 +/- 0.0036 in plasma from normal volunteers (p less than 0.0009; t test). Etoposide binding ratio (BR) was correlated directly with SA (r2 = 0.83; p less than 0.05). In the population with cancer Fu was significantly correlated with bilirubin (r2 = 0.837; p less than 0.05). In a multivariate analysis, SA and bilirubin were significant predictors of Fu (r2 = 0.93; p less than 0.05). This study corroborates previous reports of etoposide PB in normal human serum and demonstrates altered PB in patients with abnormal serum albumin or bilirubin levels.
Stewart
C F
CF
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee, Memphis 38163.
Pieper
J A
JA
Arbuck
S G
SG
Evans
W E
WE
D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D005047:Etoposide / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood*; D011485:Protein Binding; D012709:Serum Albumin / Q000032:analysis
D001798:Blood Proteins; D012709:Serum Albumin; D005047:Etoposide; D001663:Bilirubin