Li, Jianguo, Lovern, Mark, Green, Michelle L, Chiu, Joannellyn, Zhou, Diansong, Comisar, Craig, Xiong, Yuan, Hing, Jeremy, MacPherson, Merran, Wright, James G et al (show 3 more authors)
(2019)
Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE, 12 (2).
pp. 151-163.
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Abstract
Ceftazidime-avibactam is a novel β-lactam/β-lactamase inhibitor combination for the treatment of serious infections caused by resistant gram-negative pathogens. Population pharmacokinetic (PopPK) models were built to incorporate pharmacokinetic (PK) data from five phase III trials in patients with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI), or nosocomial (including ventilator-associated) pneumonia. Ceftazidime and avibactam pharmacokinetics were well-described by two-compartment disposition models, with creatinine clearance (CrCL) the key covariate determining clearance variability. Steady-state ceftazidime and avibactam exposure for most patient subgroups differed by ≤ 20% vs. healthy volunteers. Probability of PK/pharmacodynamic (PD) target attainment (free plasma ceftazidime > 8 mg/L and avibactam > 1 mg/L for ≥ 50% of dosing interval) was ≥ 94.9% in simulations for all patient subgroups, including indication and renal function categories. No exposure-microbiological response relationship was identified because target exposures were achieved in almost all patients. These modeling results support the approved ceftazidime-avibactam dosage regimens (2000-500 mg every 8 hours, adjusted for CrCL ≤ 50 mL/min).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Urinary Tract Infections, Ceftazidime, Creatinine, Drug Combinations, Anti-Bacterial Agents, Dose-Response Relationship, Drug, Models, Biological, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Pneumonia, Ventilator-Associated, Clinical Trials, Phase III as Topic, Azabicyclo Compounds, Young Adult, Datasets as Topic, Renal Elimination |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 17 Sep 2018 15:00 |
| Last Modified: | 19 Jan 2023 01:17 |
| DOI: | 10.1111/cts.12585 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3026400 |
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