Pharmacokinetics and Pharmacodynamics of beta-Lactamase Inhibitors.

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Crass RL, Pai MP

Pharmacokinetics and Pharmacodynamics of beta-Lactamase Inhibitors.

Pharmacotherapy. 2019 Feb;39(2):182-195. doi: 10.1002/phar.2210. Epub 2019 Jan 20.

PubMed ID
30589457 [ View in PubMed
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Abstract

Novel beta-lactamase inhibitors have extended the reach of new and existing beta-lactams against multidrug-resistant bacteria expressing beta-lactamases. The efficacy of these combination therapeutics relies on a complex two-component pharmacodynamic (PD) system where the beta-lactamase inhibitor inactivates the bacterial beta-lactamase enzyme and frees the companion beta-lactam to act against its penicillin-binding protein target. Despite considerable investigation into the pharmacokinetics (PK) and pharmacodynamics of beta-lactams, the pharmacology of their companion beta-lactamase inhibitors has only recently been rigorously explored. This review describes the diversity of beta-lactamase enzymes, mechanisms of enzyme inhibition, and factors impacting the efficacy of clinically available beta-lactamase inhibitors. Relevant PK differences among available inhibitors and the PK/PD properties of these agents are described independently of their companion beta-lactams. In the modern era of antibiotic resistance, a comprehensive understanding of the pharmacology, PK, and PD of beta-lactamase inhibitors is paramount to maximizing the therapeutic efficacy of existing beta-lactam/beta-lactamase inhibitor combinations and protecting novel agents in the drug development pipeline.

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