Pharmacokinetics of polymyxin drugs in special populations

The rising incidence of multidrug-resistant Gram-negative infections has reaffirmed the importance of polymyxins (polymyxin B (PMB), colistin methanesulfonate (CMS), and colistin sulfate (CS)) as essential last-line treatments. This review assesses the pharmacokinetic (PK) and population pharmacokinetic (PopPK) data for polymyxins in special populations, aiming to establish agent-specific PK profiles and optimize dosing strategies. A total of 72 articles published between 2005 and 2025 were reviewed, with 36 focusing on the PK of PMB, 30 on CMS, and 6 on CS. PopPK analyses constituted the majority of the included studies. The review reveals that polymyxin pharmacokinetics exhibit substantial variability across special patient groups. Key findings include an increased voxlume of distribution in critically ill patients and the identification of renal function as a major covariate influencing polymyxins PK. Altered drug clearance in patients receiving renal replacement therapies (e.g., CRRT and IHD), while body weight influences distribution in obese individuals. Distinct PK profiles were also identified in patient populations such as pediatrics, the elderly, burn victims, those on ECMO, and those with cystic fibrosis. These conditions contribute to significant variability in drug exposure, underscoring the need for model-informed precision dosing (MIPD) combined with therapeutic drug monitoring (TDM) to optimize efficacy and minimize toxicity in these vulnerable populations.