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Altered protein binding of etoposide in patients with cancer
Author(s) -
Stewart Clinton F,
Pieper John A,
Arbuck Susan G,
Evans William E
Publication year - 1989
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1989.8
Subject(s) - etoposide , bilirubin , albumin , serum albumin , medicine , population , blood proteins , cancer , cancer chemotherapy , chemistry , endocrinology , pharmacology , chemotherapy , environmental health
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/m 2 ) and in plasma of 14 volunteers was determined by equilibrium dialysis with 3 H‐etoposide. The unbound fraction (F u ) in patients with cancer was 0.139 ± 0.099 compared with 0.043 ± 0.0036 in plasma from normal volunteers (p < 0.0009; t test). Etoposide binding ratio (BR) was correlated directly with SA ( r 2 = 0.83; p < 0.05). In the population with cancer F u was significantly correlated with bilirubin ( r 2 = 0.837; p < 0.05). In a multivariate analysis, SA and bilirubin were significant predictors of F u ( r 2 = 0.93; p < 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. Clinical Pharmacology and Therapeutics (1989) 45, 49–55; doi: 10.1038/clpt.1989.8