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

To 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...

Full description

Saved in:
Bibliographic Details
Main Authors: Shilei Yang (Author), Zhihao Liu (Author), Changyuan Wang (Author), Shijie Wen (Author), Qiang Meng (Author), Xiaokui Huo (Author), Huijun Sun (Author), Xiaodong Ma (Author), Jinyong Peng (Author), Zhonggui He (Author), Kexin Liu (Author)
Format: Book
Published: Elsevier, 2019-11-01T00:00:00Z.
Subjects:
Online Access:Connect to this object online.
Tags: Add Tag
No Tags, Be the first to tag this record!

MARC

LEADER 00000 am a22000003u 4500
001 doaj_8a1d5a9f17ac44eb99f0173f4d764cfd
042 |a dc 
100 1 0 |a Shilei Yang  |e author 
700 1 0 |a Zhihao Liu  |e author 
700 1 0 |a Changyuan Wang  |e author 
700 1 0 |a Shijie Wen  |e author 
700 1 0 |a Qiang Meng  |e author 
700 1 0 |a Xiaokui Huo  |e author 
700 1 0 |a Huijun Sun  |e author 
700 1 0 |a Xiaodong Ma  |e author 
700 1 0 |a Jinyong Peng  |e author 
700 1 0 |a Zhonggui He  |e author 
700 1 0 |a Kexin Liu  |e author 
245 0 0 |a Piperacillin enhances the inhibitory effect of tazobactam on β-lactamase through inhibition of organic anion transporter 1/3 in rats 
260 |b Elsevier,   |c 2019-11-01T00:00:00Z. 
500 |a 1818-0876 
500 |a 10.1016/j.ajps.2018.11.003 
520 |a To 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% when the two drugs were coadministered. Keywords: Organic anion transporter, Piperacillin, Tazobactam, Drug-drug interaction 
546 |a EN 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Asian Journal of Pharmaceutical Sciences, Vol 14, Iss 6, Pp 677-686 (2019) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S1818087618309139 
787 0 |n https://doaj.org/toc/1818-0876 
856 4 1 |u https://doaj.org/article/8a1d5a9f17ac44eb99f0173f4d764cfd  |z Connect to this object online.