Abstract | BACKGROUND: OBJECTIVE: This study aimed to evaluate the roles of renal uptake and efflux transporters in the excretion of meropenem and potential drug interactions mediated by renal drug transporters. METHODS: RESULTS: We observed that meropenem was a low-affinity substrate of OAT1/3 and had a weak inhibitory effect on OAT1/3 and MATE2K. BCRP, MDR1, MRP2, MATE1, and MATE2K could not mediate renal excretion of meropenem. Moreover, meropenem was not an inhibitor of BCRP, MDR1, MRP2, or MATE1. Among five tested antibiotics, moderate inhibition on OAT3-mediated meropenem uptake was observed for linezolid (IC50 value was 69.2 μM), weak inhibition was observed for piperacillin, benzylpenicillin, and tazobactam (IC50 values were 282.2, 308.0 and 668.1 μM, respectively), and no inhibition was observed for sulbactam. Although piperacillin had a relatively high drug-drug interaction index (ratio of maximal unbound plasma concentration to IC50 was 1.42) in vitro, no meaningful impact was reported on the pharmacokinetics of meropenem in rats. CONCLUSION: Our results indicated that clinically significant interactions between meropenem and these five antibiotics are low.
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Authors | Jing Dong, Yanhui Liu, Longxuan Li, Yunhe Ding, Jun Qian, Zheng Jiao |
Journal | Current drug metabolism
(Curr Drug Metab)
Vol. 23
Issue 5
Pg. 423-431
(08 03 2022)
ISSN: 1875-5453 [Electronic] Netherlands |
PMID | 35490314
(Publication Type: Journal Article)
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Copyright | Copyright© Bentham Science Publishers; For any queries, please email at [email protected]. |
Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- ATP Binding Cassette Transporter, Subfamily G, Member 2
- Anti-Bacterial Agents
- Membrane Transport Proteins
- Neoplasm Proteins
- Organic Anion Transporters
- Organic Anion Transporters, Sodium-Independent
- Meropenem
- Piperacillin
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(metabolism)
- ATP Binding Cassette Transporter, Subfamily G, Member 2
(metabolism)
- Animals
- Anti-Bacterial Agents
(metabolism, pharmacology)
- Drug Interactions
- Humans
- Kidney
(metabolism)
- Membrane Transport Proteins
(metabolism)
- Meropenem
(metabolism, pharmacology)
- Neoplasm Proteins
(metabolism)
- Organic Anion Transporters
- Organic Anion Transporters, Sodium-Independent
(metabolism)
- Piperacillin
(metabolism)
- Rats
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