The pharmacokinetic study on enhanced vancomycin renal clearance in patients with malignancies.

最近有报道称，恶性肿瘤患者的万古霉素(VCM)总清除量(CLtot)明显高于非恶性肿瘤患者。在本研究中，为了阐明VCM CLtot在恶性肿瘤中的增强机制，我们采用群体药代动力学分析和大鼠化学致癌物诱导的骨肉瘤动物模型，将其移植到大腿肌肉中。荷瘤大鼠VCM的CLtot和肾清除量(CLR)均高于对照组。但肾小球滤过率无明显差异。荷瘤大鼠血浆细胞因子浓度升高。当细胞因子同时作用于肾近端小管上皮(RPTEC)细胞时，VCM分泌率显著增加。这些发现提示，VCM肾小管分泌或细胞因子重吸收的改变可能与荷瘤大鼠的VCM CLtot增强有关。

Recently, it has been reported that vancomycin (VCM) total clearance (CLtot) is significantly higher in patients with malignancies compared to those without malignancies. In the present study, to clarify the mechanism of VCM CLtot enhancement in malignancy, we adopted the population pharmacokinetic analysis and the rat animal models, using chemical carcinogen-induced osteosarcoma, transplanted into thigh muscles. The CLtot and renal clearance (CLr) of VCM in the tumor-bearing rats were increased compared to that of the control rats. However, there was no difference in the glomerular filtration rate. The plasma concentrations of cytokines, were elevated in tumor-bearing rats. When cytokines were simultaneously exposed to renal proximal tubular epithelial (RPTEC) cells, VCM secretory ratio increased significantly. These findings suggest that the change in VCM tubular secretion or reabsorption by cytokines might be associated with the VCM CLtot enhancement in the tumor-bearing rats.