Use of pharmacokinetic/pharmacodynamic approaches for dose optimization: a case study of plazomicin.

Autor: Luterbach CL; Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Chapel Hill, NC, United States; Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, United States., Rao GG; Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Chapel Hill, NC, United States. Electronic address: gaurirao@live.unc.edu.
Jazyk: angličtina
Zdroj: Current opinion in microbiology [Curr Opin Microbiol] 2022 Dec; Vol. 70, pp. 102204. Date of Electronic Publication: 2022 Sep 16.
DOI: 10.1016/j.mib.2022.102204
Abstrakt: With limited treatment options available for multidrug-resistant bacteria, dose optimization is critical for achieving effective drug concentrations at the site of infection. Yet, selecting an appropriate dose and appropriate time to administer the dose with dosing frequency requires extensive understanding of the interplay between drug pharmacokinetics/pharmacodynamics (PK/PD), the host immune system, and bacterial-resistant mechanisms. Model-informed dose optimization (MIDO) uses PK/PD models (e.g. population PK, mechanism-based models, etc.) that incorporate preclinical and clinical data to simulate/predict performance of treatment regimens in appropriate patient populations and/or infection types that may not be well-represented in clinical trials. Here, we highlight the stages of a MIDO approach for designing optimized regimens by reviewing current clinical, preclinical, and PK/PD modeling data available for plazomicin. Plazomicin is an aminoglycoside approved in 2018 for the treatment of complicated urinary tract infections in adults. Applying knowledge gained by PK/PD modeling can guide therapeutic drug monitoring to ensure that drug exposure is appropriate for clinical efficacy while limiting drug-related toxicity.
(Copyright © 2022. Published by Elsevier Ltd.)
Databáze: MEDLINE
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