Objective: To probe into the correlation between nephrotoxicity of vancomycin (VCM) in mice and administration time and its mechanism of action. Methods: Twenty-five male C57BL/6 mice were randomly divided into the VCM (600 mg/kg

intraperitoneal injection

qd) 1 d group

VCM 3 d group

VCM 7 d group

VCM 10 d group and blank control group (normal saline)

with 5 mice in each group. The kidney weight of each group was weighed after the last administration of 24 h. The levels of creatinine and urea nitrogen in serum of mice were determined by the automatic biochemical analyzer. The morphological and structural changes of kidney tissues were observed by hematoxylin-eosin staining. The concentrations of VCM in serum and kidney of mice were determined by liquid chromatography-mass spectrometer (LC-MS). The mRNA expression of transporter-related genes in kidney was analyzed by real-time polymerase chain reaction (PCR). Results: Compared with the blank control group

VCM significantly increased the kidney weight

induced the kidney function damage and kidney pathological changes in a time dependent manner. After 3 d of VCM administration

there was slight accumulation in the kidney. After 7 d of VCM administration

VCM was highly accumulated in the kidney and serum. After intraperitoneal injection of VCM

the mRNA levels of organic cation transporter 2 (Oct2) and multidrug resistance associated protein 2 (Mrp2) in the early kidney were up-regulated

the mRNA levels of Oct1

Oct2

multidrug and toxin-excreting protein 1 (Mate1)

organic anion transporter 1 (Oat1)

Oat3 and Mrp2 in the middle and late kidney decreased significantly

while the mRNA levels of Mrp4 were not significantly changed. Conclusion: The mechanism of action of VCM may be related to the effects on kidney transporter expression as it starts to induce kidney damage 3 d after intraperitoneal administration

and there is drug accumulation in the kidney.