Population Pharmacokinetics of Intravenous Polymyxin B from Clinical Samples

Antimicrobial Agents and Chemotherapy
Christine J KubinMichael T Yin

Abstract

A retrospective study was conducted in hospitalized patients receiving intravenous polymyxin B who underwent therapeutic drug monitoring during treatment. The aim of this study was to assess the population pharmacokinetics (PK) of intravenous polymyxin B in patients with variable total body weights and create a population model for clinical use. Nonlinear mixed-effects modeling analyses were performed. A total of 43 patients were included, and 70% of these patients were male. The median age was 58 years, and the median weight was 78 kg. The median polymyxin B dose was 180 mg/day or 2.8 mg/kg/day. A one-compartment model described the polymyxin B PK well with conditional mean parameter estimates of a clearance (CL) of 2.37 liters/h and a volume of distribution of 34.4 liters and can be employed for clinical population modeling. Total body weight was not significantly associated with CL (Akaike information criterion, 361.6 for the weight-based model versus 359.5 for the non-weight-based model). These data suggest that dosing according to patient body weight requires further exploration. Greater study is needed to assess the relationships between polymyxin B exposures and efficacy and toxicity.

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Citations

Jan 10, 2018·Antimicrobial Agents and Chemotherapy·Cristina MiglisMarc H Scheetz
Apr 12, 2019·The Annals of Pharmacotherapy·Yarelis Alvarado ReyesWilliam R Wolowich
Mar 27, 2019·Antibiotics·Sean N AvedissianMarc H Scheetz
May 10, 2020·Intensive Care Medicine·Mohd H Abdul-AzizUNKNOWN Infections in the ICU and Sepsis Working Group of International Society of Antimicrobial Chemotherapy (ISAC)
Jul 27, 2021·Journal of Pharmaceutical and Biomedical Analysis·Maksim A BurkinSergei V Tsarenko
Aug 4, 2021·European Journal of Clinical Pharmacology·Ya-Qian LiQi Pei
Nov 24, 2021·CPT: Pharmacometrics & Systems Pharmacology·Patrick O HanafinGauri G Rao

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