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Impact of Piperacillin Unbound Fraction Variability on Dosing Recommendations in Critically Ill Patients
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  • Ibrahim El-Haffaf,
  • Romain Guilhaumou,
  • Lionel Velly,
  • Amélie Marsot
Ibrahim El-Haffaf
Université de Montréal

Corresponding Author:[email protected]

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Romain Guilhaumou
Hopital de la Timone, APHM
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Lionel Velly
Hôpital de la Timone service d'anesthésie réanimation 1
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Amélie Marsot
Université de Montréal
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A common approach to assess the efficacy of piperacillin is to firstly measure the total concentration, and to afterwards apply a theoretical unbound fraction of 70% to obtain the unbound concentration. However, hypoalbuminemia is a common phenomenon in critically ill patients, resulting in variations in unbound fraction. Therefore, we aimed to simulate the impact of piperacillin unbound fraction fluctuations on the predictive performance of a population pharmacokinetic model and on dosing recommendations of piperacillin. Unbound factors of 70, 75, 80 and 85% were applied to total concentrations of piperacillin administered by continuous infusion from an external dataset. A validated model was used for assessment of predictive performance and to estimate patient clearance. Dosing simulations were performed to evaluate target attainment. Variation in unbound fraction caused minimal impact on piperacillin clearance and target attainment but revealed to influence model evaluation.
02 Aug 2022Submitted to British Journal of Clinical Pharmacology
05 Aug 2022Submission Checks Completed
05 Aug 2022Assigned to Editor
23 Aug 2022Reviewer(s) Assigned
07 Sep 2022Review(s) Completed, Editorial Evaluation Pending
22 Sep 2022Editorial Decision: Revise Major
21 Nov 20221st Revision Received
22 Nov 2022Submission Checks Completed
22 Nov 2022Assigned to Editor
22 Nov 2022Review(s) Completed, Editorial Evaluation Pending
22 Nov 2022Editorial Decision: Accept
15 Dec 2022Published in British Journal of Clinical Pharmacology. 10.1111/bcp.15619