Nichols, Wright W, Newell, Paul, Critchley, Ian A, Riccobene, Todd and Das, Shampa 
ORCID: 0000-0002-2540-4816
(2018)
Avibactam Pharmacokinetic/Pharmacodynamic Targets.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 62 (6).
e02446-e02417.
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Abstract
Avibactam is a novel non-β-lactam β-lactamase inhibitor that has been approved in the United States and Europe for use in combination with ceftazidime. Combinations of avibactam with aztreonam or ceftaroline fosamil have also been clinically evaluated. Until recently, there has been very little precedence of which pharmacokinetic/pharmacodynamic (PK/PD) indices and magnitudes are appropriate to use for β-lactamase inhibitors in population PK modeling for analyzing potential doses and susceptibility breakpoints. For avibactam, several preclinical studies using different <i>in vitro</i> and <i>in vivo</i> models have been conducted to identify the PK/PD index of avibactam and the magnitude of exposure necessary for effect in combination with ceftazidime, aztreonam, or ceftaroline fosamil. The PD driver of avibactam critical for restoring the activity of all three partner β-lactams was found to be time dependent rather than concentration dependent and was defined as the time that the concentration of avibactam exceeded a critical concentration threshold (%<i>f</i>T>C<sub>T</sub>). The magnitude of the C<sub>T</sub> and the time that this threshold needed to be exceeded to elicit particular PD endpoints varied depending on the model and the partner β-lactam. This review describes the preclinical studies used to determine the avibactam PK/PD target in combination with its β-lactam partners.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | avibactam, diazabicyclooctane, BL-BLI, PK/PD |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 07 Jun 2018 15:33 |
| Last Modified: | 07 Feb 2024 13:19 |
| DOI: | 10.1128/AAC.02446-17 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3022295 |
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