Altered protein binding of etoposide in patients with cancer

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Abstract
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 < 0.0009; t test). Etoposide binding ratio (BR) was correlated directly with SA (r2 = 0.83; p < 0.05). In the population with cancer Fu was significantly correlated with bilirubin (r2 = 0.837; p < 0.05). In a multivariate analysis, SA and bilirubin were significant predictors of Fu (r2 = 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