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Pharmacokinetics and Target Attainment of ß-lactam Antibiotics in Older People: A Systematic Review of Current Literature

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Abstract

Background and objective

(Patho)physiological changes in older people may influence the pharmacokinetics (PK), and consequently the target attainment, of ß-lactam antibiotics using standard dosing regimens. This systematic review compiles the current knowledge on the PK and target attainment of ß-lactam antibiotics in older people, with the aim to identify priorities for dose optimization in this patient population.

Methods

A systematic literature search of the PubMed and EMBASE databases was conducted. Relevant articles published prior to 1 December 2021 were identified as eligible when they included data on the PK of ß-lactam antibiotics in adults ≥ 65 years of age. Extracted information included reported PK parameters (volume of distribution, clearance [CL], elimination rate constant, intercompartmental CL, elimination half-life, area under the concentration-time curve, maximum and trough concentration), covariates on PK parameters, target attainment rate, and dosing recommendations.

Results

Ninety-one relevant articles were included in this review. Four main ß-lactam subclasses were represented: 59.3% on cephalosporins + cephamycins, 25.3% on penicillins, 15.4% on carbapenems, and 3.3% on monobactams; 65.9% of articles involved intravenous administration, 16.5% mixed administration routes, 12.1% oral administration, and 5.5% intramuscular administration. The majority of studies had a small sample size, often did not include detailed information on the study population and methods, and were fairly old. CL was, on average, decreased, while elimination half-life was prolonged in aged subjects compared with young subjects. Volume of distribution was generally similar between age groups. Most studies identified renal function as the most important contributor to altered drug CL. In only 30.8% of the articles, target attainment was studied, and in 35.7% of these articles, target attainment was found to be suboptimal. Dosing recommendations were incorporated in 87.9% of articles.

Conclusion

Studies frequently fail to provide an evidence-based dosing recommendation for this diverse patient population. Model-based PK studies that address both physiological and disease-related changes are urgently needed. This review identified gaps of knowledge to set priorities for further research.

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  1. Jeroen Vervalcke and Arnaud De Clercq shared first authorship on this work.

Authors and Affiliations

  1. Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

    Jeroen Vervalcke & Arnaud De Clercq

  2. Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium

    Peter De Paepe & Pieter A. De Cock

  3. Department of Emergency Medicine, Ghent University Hospital, Ghent, Belgium

    Peter De Paepe & Tania Desmet

  4. Section of Geriatrics, Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium

    Mirko Petrovic

  5. Department of Pharmacy, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium

    Pieter A. De Cock

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  1. Jeroen Vervalcke
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Jeroen Vervalcke, Arnaud De Clercq, Peter De Paepe, Mirko Petrovic, Tania Desmet, and Pieter A. De Cock declare they have no conflicts of interest in relation to this article.

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PADC, PDP, MP and TD provided the concept for this systematic review. JV, ADC and PADC performed the literature search and data analysis. JV, ADC, and PADC drafted the original manuscript, and PDP, MP and TD critically reviewed and edited the manuscript.

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Vervalcke, J., De Clercq, A., De Paepe, P. et al. Pharmacokinetics and Target Attainment of ß-lactam Antibiotics in Older People: A Systematic Review of Current Literature. Clin Pharmacokinet 62, 1–43 (2023). https://doi.org/10.1007/s40262-022-01196-1

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