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Population pharmacokinetics of continuous infusion of piperacillin in critically ill patients.
- Source :
-
International journal of antimicrobial agents [Int J Antimicrob Agents] 2018 Apr; Vol. 51 (4), pp. 594-600. Date of Electronic Publication: 2017 Dec 22. - Publication Year :
- 2018
-
Abstract
- Dosing recommendations for continuous infusion of piperacillin, a broad-spectrum beta-lactam antibiotic, are mainly guided by outputs from population pharmacokinetic models constructed with intermittent infusion data. However, the probability of target attainment in patients receiving piperacillin by continuous infusion may be overestimated when drug clearance estimates from population pharmacokinetic models based on intermittent infusion data are used, especially when higher doses (e.g. 16 g/24 h or more) are simulated. Therefore, the purpose of this study was to describe the population pharmacokinetics of piperacillin when infused continuously in critically ill patients. For this analysis, 270 plasma samples from 110 critically ill patients receiving piperacillin were available for population pharmacokinetic model building. A one-compartment model with linear clearance best described the concentration-time data. The mean ± standard deviation parameter estimates were 8.38 ± 9.91 L/h for drug clearance and 25.54 ± 3.65 L for volume of distribution. Creatinine clearance improved the model fit and was supported for inclusion as a covariate. In critically ill patients with renal clearance higher than 90 mL/min/1.73 m <superscript>2</superscript> , a high-dose continuous infusion of 24 g/24 h is insufficient to achieve adequate exposure (pharmacokinetic/pharmacodynamic target of 100% fT <subscript>>4 x MIC</subscript> ) against susceptible Pseudomonas aerginosa isolates (MIC ≤16 mg/L). These findings suggest that merely increasing the dose of piperacillin, even with continuous infusion, may not always result in adequate piperacillin exposure. This should be confirmed by evaluating piperacillin target attainment rates in critically ill patients exhibiting high renal clearance.<br /> (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)
- Subjects :
- Anti-Bacterial Agents administration & dosage
Anti-Bacterial Agents pharmacokinetics
Anti-Bacterial Agents therapeutic use
Creatinine blood
Drug Combinations
Female
Humans
Infusions, Intravenous
Kidney Function Tests
Male
Metabolic Clearance Rate
Microbial Sensitivity Tests
Middle Aged
Penicillanic Acid therapeutic use
Piperacillin blood
Pseudomonas Infections microbiology
Pseudomonas aeruginosa drug effects
Sepsis microbiology
Tazobactam
Critical Illness therapy
Penicillanic Acid analogs & derivatives
Piperacillin pharmacokinetics
Piperacillin therapeutic use
Pseudomonas Infections drug therapy
Sepsis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7913
- Volume :
- 51
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of antimicrobial agents
- Publication Type :
- Academic Journal
- Accession number :
- 29277531
- Full Text :
- https://doi.org/10.1016/j.ijantimicag.2017.12.015