顺铂治疗期间的微量白蛋白尿：与药代动力学的关系及对肾保护的意义。

Microalbuminuria during cisplatin therapy: relation with pharmacokinetics and implications for nephroprotection.

作者信息

Kern W, Braess J, Kaufmann C C, Wilde S, Schleyer E, Hiddemann W

机构信息

University Hospital Grosshadern, Department of Medicine III, Ludwig-Maximilians-University, München, Germany.

出版信息

Anticancer Res. 2000 Sep-Oct;20(5C):3679-88.

PMID:11268439

Abstract

BACKGROUND

To assess the relation of cisplatin-induced nephrotoxicity to its pharmacology.

PATIENTS AND METHODS

In 22 chemonaive patients (median age, 32 years) receiving 100-150 mg/m2 cisplatin for a total of 54 courses of therapy pharmacokinetics of ultra-filtrable platin were analyzed. Nephrotoxicity was sensitively assessed by nephelometric analyses of urinary marker-proteins.

RESULTS

The parameters calculated for ultrafiltrable platin were (two-compartment-model): terminal half-life, 36 hours (coefficient of variation [CV], 22%); AUC, 12852 ng h/ml (33%); volume of distribution, 3531 (44%); total clearance, 285 ml/min (30%); renal clearance, 149 ml/min (23%); maximum concentration, 1720 ng/ml (66%); renal elimination, 57% of applied dose (26%). A pathological urinary excretion of albumin > 20 mg/l and alpha-1-microglobulin > 10 mg/l was detected in 39 out of 54 and 42 out of 54 cycles, respectively. The degree of albuminuria was related with urinary monoaquoplatin concentrations (p = 0.003).

CONCLUSION

Nephrotoxicity of cisplatin appears to depend on the urinary monoaquoplatin concentrations which may be modulated by application of saline.

摘要

背景

评估顺铂诱导的肾毒性与其药理学之间的关系。

患者与方法

对22例初治患者（中位年龄32岁）进行分析，这些患者接受100 - 150mg/m²顺铂治疗，共54个疗程，分析超滤液中铂的药代动力学。通过对尿标志物蛋白的比浊分析灵敏地评估肾毒性。

结果

超滤液中铂计算出的参数（二室模型）为：终末半衰期36小时（变异系数[CV]，22%）；曲线下面积（AUC），12852ng·h/ml（33%）；分布容积，3531（44%）；总清除率，285ml/min（30%）；肾清除率，149ml/min（23%）；最大浓度，1720ng/ml（66%）；肾排泄量，给药剂量的57%（26%）。在54个疗程中的39个和42个疗程中，分别检测到白蛋白病理性尿排泄>20mg/l和α1 - 微球蛋白>10mg/l。蛋白尿程度与尿中一水合铂浓度相关（p = 0.003）。