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

ElsevierVolume 70, December 2022, 102204Current Opinion in MicrobiologyHighlights•

Pharmacokinetics/pharmacodynamics of plazomicin has been characterized across a broad range of multidrug resistant pathogens.

Animal models show that bacterial clearance by plazomicin is aided by the host immune system (i.e. granulocyte killing).

Dose optimization of plazomicin may be especially relevant for patients with renal impairment to minimize nephrotoxicity.

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.

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© 2022 Published by Elsevier Ltd.

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