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

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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.