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Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups.


ABSTRACT: Ceftazidime-avibactam is a novel ?-lactam/?-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).

SUBMITTER: Li J 

PROVIDER: S-EPMC6440567 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups.

Li Jianguo J   Lovern Mark M   Green Michelle L ML   Chiu Joannellyn J   Zhou Diansong D   Comisar Craig C   Xiong Yuan Y   Hing Jeremy J   MacPherson Merran M   Wright James G JG   Riccobene Todd T   Carrothers Timothy J TJ   Das Shampa S  

Clinical and translational science 20180928 2


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  ...[more]

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