We have located links that may give you full text access.
Role of transporters in the disposition of a novel β-lactamase inhibitor: relebactam (MK-7655).
Journal of Antimicrobial Chemotherapy 2019 March 20
OBJECTIVES: To identify the transporters involved in renal elimination of relebactam, and to assess the potential of relebactam as a perpetrator or victim of drug-drug interactions (DDIs) for major drug transporters.
METHODS: A series of bidirectional transport, uptake and inhibition studies were conducted in vitro using transfected cell lines and membrane vesicles. The inhibitory effects of relebactam on major drug transporters, as well as the inhibitory effects of commonly used antibiotics/antifungals on organic anion transporter (OAT) 3-mediated uptake of relebactam, were assessed.
RESULTS: Relebactam was shown to be a substrate of OAT3, OAT4, and multidrug and toxin extrusion (MATE) proteins MATE1 and MATE2K. Relebactam did not show profound inhibition across a panel of transporters, including organic anion-transporting polypeptides 1B1 and 1B3, OAT1, OAT3, organic cation transporter 2, MATE1, MATE2K, breast cancer resistance protein, multidrug resistance protein 1 and the bile salt export pump. Among the antibiotics/antifungals assessed for potential DDIs, probenecid demonstrated the most potent in vitro inhibition of relebactam uptake; however, such in vitro data did not translate into clinically relevant DDIs, suggesting that relebactam can be co-administered with OAT inhibitors, such as probenecid.
CONCLUSIONS: Overall, relebactam has low potential to be a victim or perpetrator of DDIs with major drug transporters.
METHODS: A series of bidirectional transport, uptake and inhibition studies were conducted in vitro using transfected cell lines and membrane vesicles. The inhibitory effects of relebactam on major drug transporters, as well as the inhibitory effects of commonly used antibiotics/antifungals on organic anion transporter (OAT) 3-mediated uptake of relebactam, were assessed.
RESULTS: Relebactam was shown to be a substrate of OAT3, OAT4, and multidrug and toxin extrusion (MATE) proteins MATE1 and MATE2K. Relebactam did not show profound inhibition across a panel of transporters, including organic anion-transporting polypeptides 1B1 and 1B3, OAT1, OAT3, organic cation transporter 2, MATE1, MATE2K, breast cancer resistance protein, multidrug resistance protein 1 and the bile salt export pump. Among the antibiotics/antifungals assessed for potential DDIs, probenecid demonstrated the most potent in vitro inhibition of relebactam uptake; however, such in vitro data did not translate into clinically relevant DDIs, suggesting that relebactam can be co-administered with OAT inhibitors, such as probenecid.
CONCLUSIONS: Overall, relebactam has low potential to be a victim or perpetrator of DDIs with major drug transporters.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app