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Pharmacokinetics and Pharmacodynamics of β‐Lactamase Inhibitors
Author(s) -
Crass Ryan L.,
Pai Manjunath P.
Publication year - 2019
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.2210
Subject(s) - pharmacodynamics , pharmacology , pharmacokinetics , antibiotics , beta lactamase inhibitors , medicine , chemistry , computational biology , biology , microbiology and biotechnology
Novel β‐lactamase inhibitors have extended the reach of new and existing β‐lactams against multidrug‐resistant bacteria expressing β‐lactamases. The efficacy of these combination therapeutics relies on a complex two‐component pharmacodynamic (PD) system where the β‐lactamase inhibitor inactivates the bacterial β‐lactamase enzyme and frees the companion β‐lactam to act against its penicillin‐binding protein target. Despite considerable investigation into the pharmacokinetics (PK) and pharmacodynamics of β‐lactams, the pharmacology of their companion β‐lactamase inhibitors has only recently been rigorously explored. This review describes the diversity of β‐lactamase enzymes, mechanisms of enzyme inhibition, and factors impacting the efficacy of clinically available β‐lactamase inhibitors. Relevant PK differences among available inhibitors and the PK/PD properties of these agents are described independently of their companion β‐lactams. In the modern era of antibiotic resistance, a comprehensive understanding of the pharmacology, PK, and PD of β‐lactamase inhibitors is paramount to maximizing the therapeutic efficacy of existing β‐lactam/β‐lactamase inhibitor combinations and protecting novel agents in the drug development pipeline.