Impact of piperacillin unbound fraction variability on dosing recommendations in critically ill patients. Issue 4 (15th December 2022)

• Record Type: Journal Article
• Authors: El‐Haffaf, Ibrahim; Guilhaumou, Romain; Velly, Lionel; Marsot, Amélie
• Is Part Of: British journal of clinical pharmacology. Volume 89:Issue 4(2023)
• Page Start: 1502
• Page End: 1508
• Publication Date: 2022-12-15
• Subjects: clinical pharmacology -- critical care -- infectious diseases -- pharmacodynamics -- pharmacometrics; Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.15619
• Languages: English
• ISSNs: 0306-5251

Abstract

Abstract : A common approach to assess the efficacy of piperacillin is to first measure the total concentration and 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 the 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 fractions caused minimal impact on piperacillin clearance and target attainment but seemed to influence model validity.