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Simplified daptomycin dosing regimen for adult patients with methicillin-resistant Staphylococcus aureus infections based on population pharmacokinetic analysis.
- Source :
-
Drug metabolism and pharmacokinetics [Drug Metab Pharmacokinet] 2022 Jun; Vol. 44, pp. 100444. Date of Electronic Publication: 2022 Jan 07. - Publication Year :
- 2022
-
Abstract
- Daptomycin is used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. Current guidelines recommend higher daptomycin doses (8-10 mg/kg) for severe infections; however, pharmacokinetic (PK) and pharmacodynamic-based dosing strategies are still limited. Therefore, we designed a new optimal daptomycin dosing regimen for patients with MRSA infections using a population PK modeling approach. A total of 110 plasma concentrations from 47 adult patients who received daptomycin in general wards were enrolled for population PK modeling. The target area under the concentration-time curve/minimum inhibitory concentration (MIC) ratio, target peak/MIC ratio, and threshold of the trough concentration for safety were set to >666, >60, and 24.3 mg/L, respectively. Renal function was indicated as a significant covariate for daptomycin clearance. The simulated probability of target attainment was more than 90% at MIC values of 0.25 and 0.5 mg/L in all patients at the standard dose (6 mg/kg). In contrast, comprehensive simulation assessments recommended 10 mg/kg every 24 h in patients with creatinine clearance >60 mL/min for MIC values of 1.0 mg/L. We propose a new simplified daptomycin dosing regimen stratified by renal function and MIC values based on PK model-based simulation analyses. The proposed regimen is expected to maximize clinical efficacy and minimize adverse events.<br />Competing Interests: Declaration of competing interest None.<br /> (Copyright © 2022 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1880-0920
- Volume :
- 44
- Database :
- MEDLINE
- Journal :
- Drug metabolism and pharmacokinetics
- Publication Type :
- Academic Journal
- Accession number :
- 35462110
- Full Text :
- https://doi.org/10.1016/j.dmpk.2022.100444