Stewart C F, Fleming R A, Arbuck S G, Evans W E
Department of Clinical Pharmacy, University of Tennessee, Memphis 31863.
Cancer Res. 1990 Nov 1;50(21):6854-6.
Etoposide protein binding in cancer patients is variable and has been related mathematically to a linear model consisting of serum albumin and total bilirubin [percentage unbound = (1.4 x total bilirubin) - (6.8 x albumin) + 34.4]. In this prospective evaluation of the model, plasma samples were obtained following the administration of etoposide in 31 patients, and the unbound percentage (% unbound) of etoposide in plasma was determined by equilibrium dialysis. The mean measured % unbound was 15.3 +/- 11.6 (SD), and the mean model predicted % unbound was 16.7 +/- 10.1. The relation between predicted and measured etoposide % unbound was highly correlated (r2 = 0.92, P = 0.001). The model was precise but with a slight bias toward overpredicting % unbound (mean prediction error, 1.36%; 95% confidence interval, 0.09 to 2.6%). In patients with abnormal total bilirubin (i.e., greater than 1.5 mg/dl) or with hypoalbuminemia (i.e., less than 3.3 g/dl), the model was both precise and unbiased. These results demonstrate that etoposide % unbound can be predicted using serum albumin and total bilirubin. This model should be useful in prospectively identifying patients at increased risk of experiencing altered pharmacological effects due to altered protein binding of etoposide.
癌症患者中依托泊苷的蛋白结合情况存在差异，并且已通过数学方法与一个由血清白蛋白和总胆红素组成的线性模型相关联[未结合百分比 = (1.4×总胆红素) - (6.8×白蛋白) + 34.4]。在对该模型的这项前瞻性评估中，在31例患者给予依托泊苷后采集血浆样本，并通过平衡透析测定血浆中依托泊苷的未结合百分比（%未结合）。测得的平均%未结合为15.3±11.6（标准差），模型预测的平均%未结合为16.7±10.1。预测的和测得的依托泊苷%未结合之间的关系高度相关（r2 = 0.92，P = 0.001）。该模型较为精确，但在预测%未结合方面存在轻微的高估偏差（平均预测误差为1.36%；95%置信区间为0.09至2.6%）。在总胆红素异常（即大于1.5mg/dl）或存在低白蛋白血症（即小于3.3g/dl）的患者中，该模型既精确又无偏差。这些结果表明，依托泊苷的%未结合可以通过血清白蛋白和总胆红素进行预测。该模型在前瞻性识别因依托泊苷蛋白结合改变而有药理作用改变风险增加的患者方面应会很有用。
