Piperacillin enhances the inhibitory effect of tazobactam on β-lactamase through inhibition of organic anion transporter 1/3 in rats

Publication date: Available online 7 December 2018Source: Asian Journal of Pharmaceutical SciencesAuthor(s): Shilei Yang, Zhihao Liu, Changyuan Wang, Shijie Wen, Qiang Meng, Xiaokui Huo, Huijun Sun, Xiaodong Ma, Jinyong Peng, Zhonggui He, Kexin LiuAbstractTo assess the mechanism of the pharmacokinetic interaction between piperacillin and tazobactam, renal excretion and pharmacokinetic studies of piperacillin/tazobactam were investigated in normal and bacteremia rats. A bacteremia model was established to investigate the pharmacokinetic properties of piperacillin and tazobactam under different conditions. Renal slices were taken to examine the uptake of piperacillin and tazobactam. Pharmacokinetic studies of β-lactamase in rats were performed to study the contribution of rOat1/3 to the inhibition of tazobactam on β-lactamase. The AUC (from 2.93 ± 0.58 to 6.52 ± 1.44 mg•min/ml) and the plasma clearance (CLP) (from 2.41 ± 1.20 to 0.961 ± 0.212 ml/min/kg) of tazobactam were both altered after the intravenous coadministration of piperacillin and tazobactam in the bacteremia rats. The renal clearance (CLR) of tazobactam decreased from 1.30 ± 0.50 to 0.361 ± 0.043 ml/min/kg. In summary, there was a beneficial interaction between piperacillin and tazobactam mediated by rOat1 and rOat3. Piperacillin enhances the inhibitory effect of tazobactam on β-lactamase through the inhibition of rOat1 and rOat3 in rats. The contribution rate of rOat1/3 for the synergistic effect was 20...
Source: Asian Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Source Type: research