Population pharmacokinetics of piperacillin in plasma and subcutaneous tissue in patients on continuous renal replacement therapy
| Autor: | Anders Thorsted, Mats Bue, Steffen Christensen, Lena E. Friberg, Tomás Sou, Kristina Öbrink-Hansen, Pelle Hanberg, Anna Sophie L. Okkels, Torben L. Andersson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Continuous renal replacement therapy medicine.medical_treatment Microdialysis Infektionsmedicin Subcutaneous Tissue 0302 clinical medicine Prospective Studies 030212 general & internal medicine Modelling PK/PD Tissue distribution β-lactams Aged 80 and over education.field_of_study Bacterial Infections General Medicine Anti-Bacterial Agents Piperacillin Tazobactam Drug Combination Infectious Diseases medicine.anatomical_structure Pseudomonas aeruginosa Female medicine.drug Subcutaneous tissue Microbiology (medical) medicine.medical_specialty Infectious Medicine Continuous Renal Replacement Therapy 030106 microbiology Population Urology Models Biological 03 medical and health sciences Pharmacokinetics medicine Humans Computer Simulation Pseudomonas Infections Renal replacement therapy education PK/PD models Aged business.industry NONMEM Pharmacodynamics business Piperacillin |
| Zdroj: | Bue, M, Sou, T, Okkels, A S L, Hanberg, P, Thorsted, A, Friberg, L E, Andersson, T L, Öbrink-Hansen, K & Christensen, S 2020, ' Population pharmacokinetics of piperacillin in plasma and subcutaneous tissue in patients on continuous renal replacement therapy ', International Journal of Infectious Diseases, vol. 92, pp. 133-140 . https://doi.org/10.1016/j.ijid.2020.01.010 |
| DOI: | 10.1016/j.ijid.2020.01.010 |
| Popis: | Objectives: Piperacillin is a β-lactam antimicrobial frequently used in critically ill patients with acute kidney injury treated with continuous renal replacement therapy (CRRT). However, data regarding piperacillin tissue concentrations in this patient population are limited. A prospective observational study was conducted of free piperacillin concentrations during a single 8-h dosing interval in plasma (8 samples) and subcutaneous tissue (SCT) (13 samples), in 10 patients treated with CRRT following piperacillin 4 g given every 8 h as intermittent administration over 3 min. Methods: A population pharmacokinetic model was developed using NONMEM 7.4.3, to simulate alternative administration modes and dosing regimens. SCT concentrations were obtained using microdialysis. Piperacillin concentrations were compared to the clinical breakpoint minimum inhibitory concentration (MIC) for Pseudomonas aeruginosa (16 mg/l), with evaluation of the following pharmacokinetic/pharmacodynamics targets: 50% fT > 1 × MIC, 100% fT > 1 × MIC, and 100% fT > 4 × MIC. Results: SCT concentrations were generally lower than plasma concentrations. For the target of 50% free time (fT) > 1 × MIC and 100% fT > 1 × MIC, piperacillin 4 g every 8 h resulted in probability of target attainment (PTA) >90% in both plasma and SCT. PTA > 90% for the target of 100% fT > 4 × MIC was only achieved for continuous infusion. Conclusions: Piperacillin 4 g every 8 h is likely to provide sufficient exposure in both plasma and SCT to treat P.aeruginosa infections in critically ill patients on CRRT, given that targets of 50% fT > 1 × MIC or 100% fT > 1 × MIC are adequate. However, if a more aggressive target of 100% fT > 4 × MIC is adopted, continuous infusion is needed. |
| Databáze: | OpenAIRE |
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