Three methods to optimise polymyxin B dosing using estimated AUC after first dose: validation with the data generated by Monte Carlo simulation
Creators: name: Liu, Qingxia
name: Zhou, Jianxing
name: Zheng, You
name: Xu, Baohua
name: Li, Dandan
name: Liu, Maobai
name: Zhang, Xiaohan
name: Wu, Xuemei
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Space Science
subject: Physical Sciences not elsewhere classified
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Mathematical Sciences not elsewhere classified
subject: Marine Biology
subject: Cancer
subject: Hematology
subject: Virology
subject: Computational Biology

description: To achieve the AUC-guided dosing, we proposed three methods to estimate polymyxin B AUC across 24 h at steady state (AUC<sub>SS,24h</sub>) using limited concentrations after its first dose.Monte Carlo simulation based on a well-established population PK model was performed to generate the PK profiles of 1000 patients with normal or abnormal renal function. Polymyxin B AUC<sub>SS,24h</sub> was estimated for each subject using three methods (two-point PK approach, three-point PK approach, and four-point PK approach) based on limited concentration data in its first dose and compared with the actual AUC at steady state calculated using the linear-trapezoidal formula.In patients with normal renal function, the mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was −8.73%, 1.37%, and −0.48%, respectively. The corresponding value was −11.15%, 1.99%, and −0.28% in patients with renal impairment, respectively. The largest mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was −12.63%, −6.47%, and −0.54% when the sampling time shifted.The Excel calculators designed based on the three methods can be potentially used to optimise the dosing regimen of polymyxin B in the clinic. To achieve the AUC-guided dosing, we proposed three methods to estimate polymyxin B AUC across 24 h at steady state (AUC<sub>SS,24h</sub>) using limited concentrations after its first dose. Monte Carlo simulation based on a well-established population PK model was performed to generate the PK profiles of 1000 patients with normal or abnormal renal function. Polymyxin B AUC<sub>SS,24h</sub> was estimated for each subject using three methods (two-point PK approach, three-point PK approach, and four-point PK approach) based on limited concentration data in its first dose and compared with the actual AUC at steady state calculated using the linear-trapezoidal formula. In patients with normal renal function, the mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was −8.73%, 1.37%, and −0.48%, respectively. The corresponding value was −11.15%, 1.99%, and −0.28% in patients with renal impairment, respectively. The largest mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was −12.63%, −6.47%, and −0.54% when the sampling time shifted. The Excel calculators designed based on the three methods can be potentially used to optimise the dosing regimen of polymyxin B in the clinic.