Journal article
Population Pharmacokinetics of Piperacillin/Tazobactam Across the Adult Lifespan
Clinical pharmacokinetics, Vol.62(1), pp.127-139
01/12/2023
DOI: 10.1007/s40262-022-01198-z
PMCID: PMC9969806
PMID: 36633812
Abstract
Piperacillin/tazobactam is one of the most frequently used antimicrobials in older adults. Using an opportunistic study design, we evaluated the pharmacokinetics of piperacillin/tazobactam as a probe drug to evaluate changes in antibacterial drug exposure and dosing requirements, including in older adults.
A total of 121 adult patients were included. The population pharmacokinetic models that best characterized the observed plasma concentrations of piperacillin and tazobactam were one-compartment structural models with zero-order input and linear elimination.
Among all potential covariates, estimated creatinine clearance had the most substantial impact on the elimination clearance for both piperacillin and tazobactam. After accounting for renal function and body size, there was no remaining impact of frailty on the pharmacokinetics of piperacillin and tazobactam. Monte Carlo simulations indicated that renal function had a greater impact on the therapeutic target attainment than age, although these covariates were highly correlated. Frailty, using the Canadian Study of Health and Aging Clinical Frailty Scale, was assessed in 60 patients who were ≥ 65 years of age.
The simulations suggested that adults ≤ 50 years of age infected with organisms with higher minimum inhibitory concentrations may benefit from continuous piperacillin/tazobactam infusions (12 g/day of piperacillin component) or extended infusions of 4 g every 8 hours. However, for a target of 50% fT + minimum inhibitory concentration, dosing based on renal function is generally preferable to dosing by age, and simulations suggested that patients with creatinine clearance ≥ 120 mL/min may benefit from infusions of 4 g every 8 hours for organisms with higher minimum inhibitory concentrations.
Details
- Title: Subtitle
- Population Pharmacokinetics of Piperacillin/Tazobactam Across the Adult Lifespan
- Creators
- Marion Hemmersbach-Miller - Duke UniversityStephen J Balevic - Duke University School of MedicinePatricia L Winokur - University of IowaCornelia B Landersdorfer - Monash UniversityKenan Gu - National Institutes of HealthAustin W Chan - Duke UniversityMichael Cohen-Wolkowiez - Duke University School of MedicineThomas Conrad - Emmes (United States)Guohua An - University of IowaCarl M J Kirkpatrick - Monash UniversityGeeta K Swamy - Duke University Health SystemEmmanuel B Walter - Duke UniversityKenneth E Schmader - Duke University
- Resource Type
- Journal article
- Publication Details
- Clinical pharmacokinetics, Vol.62(1), pp.127-139
- DOI
- 10.1007/s40262-022-01198-z
- PMID
- 36633812
- PMCID
- PMC9969806
- NLM abbreviation
- Clin Pharmacokinet
- ISSN
- 0312-5963
- eISSN
- 1179-1926
- Grant note
- 5U18-FD006298 / U.S. Food and Drug Administration HHSN272201500002C / NIAID NIH HHS 5T32AI100851 / National Institute of Allergy and Infectious Diseases of the National Institutes of Health NIA P30AG028716 / National Institute on Aging, Duke Pepper Older Americans Independence Center HHSN275201000003I / NICHD NIH HHS HHSN272201500006I / National Institute of Allergy and Infectious Diseases 1U24-MD016258 / NIH HHS 1K24-AI143971 / National Institute of Allergy and Infectious Diseases HHSN272201300017I / NIAID NIH HHS HHSN2722013000201 / Vaccine and Treatment Evaluation Units (VTEU)
- Language
- English
- Date published
- 01/12/2023
- Academic Unit
- Infectious Diseases; Pharmaceutical Sciences and Experimental Therapeutics; Medicine Administration; Internal Medicine
- Record Identifier
- 9984359898302771
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