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. 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. CONCLUSIONS 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.