WellChild Laboratory, King's College London, Evelina Children's Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
Anticancer Res. 2010 Jul;30(7):2935-42.
BACKGROUND: Saracatinib (AZD0530), a potent Src inhibitor, is a subject of current evaluation as an anticancer therapy. Increased plasma creatinine levels have previously been observed after saracatinib administration in healthy subjects and this study was undertaken to characterize the underlying mechanism of this increase. SUBJECTS AND METHODS: 56 healthy male subjects were assigned to either single- (n=28; randomised to placebo or saracatinib 500 mg) or multiple-dose oral treatment (n=28; randomised to placebo or saracatinib 125 mg for 14 days). Renal function variables assessed included inulin clearance and tubular secretion of creatinine. RESULTS: Saracatinib led to a reduction in mean creatinine fractional excretion ratio, which was due to a reduction in tubular secretion of creatinine. Increased plasma creatinine was not associated with decreased glomerular filtration rate or increased creatinine production. CONCLUSION: The observed increase in plasma creatinine after saracatinib administration was due to reduced tubular secretion of creatinine, but was not considered to be clinically relevant in the context of this study.
背景：沙卡替尼（AZD0530）是一种强效的Src 抑制剂，目前正在评估其作为抗癌疗法的应用。在健康受试者中，沙卡替尼给药后曾观察到血浆肌酐水平升高，本研究旨在探讨这种升高的潜在机制。
受试者和方法：56 名健康男性受试者被分为单次（n=28；随机分配至安慰剂或沙卡替尼 500mg）或多次口服治疗（n=28；随机分配至安慰剂或沙卡替尼 125mg，共 14 天）。评估的肾功能变量包括菊粉清除率和肌酐的肾小管分泌。
结果：沙卡替尼导致平均肌酐排泄分数比降低，这是由于肌酐的肾小管分泌减少所致。血浆肌酐升高与肾小球滤过率降低或肌酐生成增加无关。
结论：在本研究中，沙卡替尼给药后观察到的血浆肌酐升高是由于肌酐的肾小管分泌减少所致，但在该研究背景下，不认为具有临床相关性。
Proc Natl Acad Sci U S A. 2011-4-4
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