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. 2025 Feb;64(2):229-241.
doi: 10.1007/s40262-024-01465-1. Epub 2024 Dec 16.

Population Pharmacokinetics of Meropenem Across the Adult Lifespan

Angelique E Boutzoukas  1   2 , Stephen J Balevic  1   2   3 , Marion Hemmersbach-Miller  4 , Patricia L Winokur  5 , Kenan Gu  6 , Austin W Chan  7 , Michael Cohen-Wolkowiez  1   2 , Thomas Conrad  8 , Guohua An  9 , Carl M J Kirkpatrick  10 , Geeta K Swamy  11 , Emmanuel B Walter  1   2   12 , Kenneth E Schmader  13   14 , Cornelia B Landersdorfer  10
Affiliations

Population Pharmacokinetics of Meropenem Across the Adult Lifespan

Angelique E Boutzoukas et al. Clin Pharmacokinet. 2025 Feb.

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.

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Conflict of interest statement

Declarations. Funding: This project was funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), US Department of Health and Human Services, through contract no. HHSN272201500002C (The EMMES Company) and a Vaccine and Treatment Evaluation Units award under contract no. HHSN272201300017I (Duke University) and contract no. HHSN2722013000201 (University of Iowa). KES also received support from the National Institute on Aging, Duke Pepper Older Americans Independence Center, NIA P30AG028716. MCW receives support for research from the NIH [1U24-MD016258], NIAID [HHSN272201500006I, HHSN272201300017I, 1K24-AI143971], Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN275201000003I], US FDA [5U18-FD006298], and industry for drug development in adults and children. This work was also supported by the NIAID of the NIH (grant number 5T32AI100851 to MHM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Conflict of Interest: AEB receives support from the NIH, the Thrasher Research Foundation, the Pediatric Trials Network (HHSN275201800003I), and the Biogen Foundation. SJB receives support from the NIH, the US Food and Drug Administration, the Childhood Arthritis and Rheumatology Research Alliance, Purdue Pharma, and consulting for UCB and Rutgers University. SJB receives support from the NIH, the Childhood Arthritis and Rheumatology Research Alliance (CARRA), consults for UCB, Rutgers University, and CARRA, and serves on an NIH data and safety monitoring board. EBW has received support from Pfizer, Moderna, Sequiris, Najit Technologies, and Clinetic as an investigator for clinical trials or studies and has served as an advisor to Vaxcyte and a consultant to Iliad Biotechnologies. The remaining authors have no relevant disclosures. Availability of Data and Material: Data are to be made available as widely as possible while safeguarding the privacy of patients and protecting confidential and proprietary data. Data can be requested from the study team. Ethics Approval: This study was approved by Duke University Health System institutional review board (IRB) Pro00083161 and University of Iowa IRB and was performed in accordance with the ethical standards set forth in the 1964 Declaration of Helsinki. Consent to Participate: A written informed consent document was used that embodied the elements of informed consent as described in the Declaration of Helsinki and adhered to the International Committee for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Harmonized Tripartite Guideline for Good Clinical Practice. Informed consent was obtained in accordance with 21 CFR 50.25 and 45 CFR 46 before any protocol-specified procedures or interventions were carried out. Participants or their legally authorized representatives provided written consent to participate in the study. Consent for Publication: Patients signed informed consent regarding the publishing of their de-identified data. They were informed that their identity will not be revealed. Code Availability: Not applicable. Author Contributions: MHM, PLW, CBL, KG, AWC, MCW, TC, GA, CMJK, GKS, EBW, and KES contributed to study conception and design of the analysis. MHM, PLW, CBL, KG, AWC, MCW, TC, GA, CMJK, GKS, EBW, and KES acquired the data. CBL performed the data analysis, including all pharmacometric modeling and simulations, and wrote the pharmacokinetic report. AEB wrote the initial draft of the manuscript; All authors interpreted the data for the work and revised the work critically for important intellectual content.

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