Journal article
Population Pharmacokinetics of Meropenem Across the Adult Lifespan
Clinical pharmacokinetics, Vol.64(2), pp.229-241
02/2025
DOI: 10.1007/s40262-024-01465-1
PMCID: PMC12181987
PMID: 39681779
Abstract
Background and Objective
We conducted an opportunistic pharmacokinetic study to evaluate the population pharmacokinetics of meropenem, an antimicrobial commonly used to treat Gram-negative infections in adults of different ages, including older adults, and determined optimal dosing regimens.
Methods
A total of 99 patients were included. The population pharmacokinetic models used had two compartments: zero-order input and linear elimination. Covariates evaluated included renal function, body size, age, sex, vasopressor use, and frailty, using the Canadian Study of Health and Aging Clinical Frailty score (in patients aged ≥ 65 years). We simulated optimal dosing regimens by renal function and by age group to achieve therapeutic target attainment.
Results
Participants’ ages ranged from 20 to 95 years, with an average age of 57.4 years, and 22% (23/103) were aged ≥ 75 years. Creatinine clearance had the greatest impact on the clearance of meropenem. After accounting for renal function and body size, no other covariates resulted in a significant impact on the pharmacokinetics of meropenem. Simulations indicated that patients with normal renal function achieved ≥ 90% target attainment only for organisms with minimum inhibitory concentrations (MICs) ≤ 4 mg/L using the least strict surrogate target of unbound concentration > MIC (fT>MIC) for 40% of the dosing interval. For the conservative target fT>4xMIC for 100% of the dosing interval, extended infusion may be required even for organisms with MICs up to 0.25 mg/L. Patients with renal impairment could achieve ≥ 90% target attainment for more resistant organisms, but extended infusion did not increase the MICs up to which target attainment could be achieved.
Conclusions
Meropenem dosing should be based on renal function rather than age. For patients without renal impairment, extended infusion may increase the probability of target attainment.
Details
- Title: Subtitle
- Population Pharmacokinetics of Meropenem Across the Adult Lifespan
- Creators
- Angelique E Boutzoukas - Duke Medical CenterStephen J Balevic - Duke Medical CenterMarion Hemmersbach-MillerPatricia L Winokur - University of IowaKenan Gu - National Institutes of HealthAustin W Chan - Duke Medical CenterMichael Cohen-Wolkowiez - Duke Medical CenterThomas Conrad - Emmes (United States)Guohua An - University of IowaCarl M J Kirkpatrick - Monash UniversityGeeta K Swamy - Duke UniversityEmmanuel B Walter - Duke University School of MedicineKenneth E Schmader - Duke UniversityCornelia B Landersdorfer - Monash University
- Resource Type
- Journal article
- Publication Details
- Clinical pharmacokinetics, Vol.64(2), pp.229-241
- DOI
- 10.1007/s40262-024-01465-1
- PMID
- 39681779
- PMCID
- PMC12181987
- NLM abbreviation
- Clin Pharmacokinet
- ISSN
- 0312-5963
- eISSN
- 1179-1926
- Publisher
- ADIS INT LTD
- Grant note
- HHSN272201500002C / NIAID NIH HHS HHSN272201300017I / NIAID NIH HHS HHSN2722013000201 / Vaccine and Treatment Evaluation Unit
- Language
- English
- Electronic publication date
- 12/16/2024
- Date published
- 02/2025
- Academic Unit
- Infectious Diseases; Pharmaceutical Sciences and Experimental Therapeutics; Medicine Administration; Internal Medicine
- Record Identifier
- 9984757746702771
Metrics
3 Record Views