Autor: |
Pau Herrero, Richard C. Wilson, Ryan Armiger, Jason A. Roberts, Alison Holmes, Pantelis Georgiou, Timothy M. Rawson |
Jazyk: |
angličtina |
Rok vydání: |
2022 |
Předmět: |
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Zdroj: |
Frontiers in Bioengineering and Biotechnology, Vol 10 (2022) |
Druh dokumentu: |
article |
ISSN: |
2296-4185 |
DOI: |
10.3389/fbioe.2022.1015389 |
Popis: |
Background and objective: Sub-therapeutic dosing of piperacillin-tazobactam in critically-ill patients is associated with poor clinical outcomes and may promote the emergence of drug-resistant infections. In this paper, an in silico investigation of whether closed-loop control can improve pharmacokinetic-pharmacodynamic (PK-PD) target attainment is described.Method: An in silico platform was developed using PK data from 20 critically-ill patients receiving piperacillin-tazobactam where serum and tissue interstitial fluid (ISF) PK were defined. Intra-day variability on renal clearance, ISF sensor error, and infusion constraints were taken into account. Proportional-integral-derivative (PID) control was selected for drug delivery modulation. Dose adjustment was made based on ISF sensor data with a 30-min sampling period, targeting a serum piperacillin concentration between 32 and 64 mg/L. A single tuning parameter set was employed across the virtual population. The PID controller was compared to standard therapy, including bolus and continuous infusion of piperacillin-tazobactam.Results: Despite significant inter-subject and simulated intra-day PK variability and sensor error, PID demonstrated a significant improvement in target attainment compared to traditional bolus and continuous infusion approaches.Conclusion: A PID controller driven by ISF drug concentration measurements has the potential to precisely deliver piperacillin-tazobactam in critically-ill patients undergoing treatment for sepsis. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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