OAT1 and OAT3 also mediate the drug-drug interaction between piperacillin and tazobactam.
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Wen S, Wang C, Duan Y, Huo X, Meng Q, Liu Z, Yang S, Zhu Y, Sun H, Ma X, Yang S, Liu K
OAT1 and OAT3 also mediate the drug-drug interaction between piperacillin and tazobactam.
Int J Pharm. 2018 Feb 15;537(1-2):172-182. doi: 10.1016/j.ijpharm.2017.12.037. Epub 2017 Dec 23.
- PubMed ID
- 29277663 [ View in PubMed]
- Abstract
This study aimed to demonstrate that organic anion transporters (OATs) mediate the drug-drug interaction (DDI) between piperacillin and tazobactam. After co-administration with piperacillin in rats, the AUC of tazobactam in plasma was significantly increased, and t1/2beta was prolonged with significant reduction in plasma clearance, renal clearance and cumulative urinary excretion. In rat and human kidney slices, probenecid, p-aminohippurate and benzylpenicillin inhibited the uptake of piperacillin and tazobactam. Piperacillin significantly inhibited the uptake of tazobactam. Moreover, the uptakes of piperacillin, tazobactam and sulbactam in hOAT1/3-HEK293 cells were significantly higher compared with mock-HEK293 cells, respectively. Piperacillin significantly inhibited the uptake of tazobactam in hOAT1/3-HEK293 cells. The Km values of tazobactam (431+/-67muM for hOAT1, 377+/-63muM for hOAT3) were significantly higher than those of piperacillin (37+/-5muM for hOAT1, 172+/-28muM for hOAT3). This suggested that piperacillin has a stronger affinity to hOAT1/3 than tazobactam. Meanwhile, the Km values of tazobactam were increased in the presence of piperacillin with unchanged Vmax. This indicated that piperacillin inhibited the uptake of tazobactam in a competitive manner. In conclusion, piperacillin and tazobactam are the substrates of hOAT1/3, and OAT1/3 mediate the DDI between piperacillin and tazobactam.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Piperacillin Solute carrier family 22 member 8 Protein Humans UnknownSubstrateDetails Tazobactam Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Tazobactam Solute carrier family 22 member 8 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
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