OAT1 and OAT3 also mediate the drug-drug interaction between piperacillin and tazobactam.

Article Details

Citation

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
DrugTransporterKindOrganismPharmacological ActionActions
PiperacillinSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
TazobactamSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
TazobactamSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
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