Polymyxin B Pharmacokinetics in Adult Cystic Fibrosis Patients

Objectives Polymyxin B pharmacokinetics ( PK ) in adults with cystic fibrosis ( CF ) are not well described. The goals of this pilot study were to identify a PK model for patients with CF receiving polymyxin B with exploration of covariate relationships of the PK parameters, to compare polymyxin B PK parameters in adults without CF , and to probe exposures associated with different dosing schemes through simulation. Methods Adult patients with CF treated with polymyxin B at New York‐Presbyterian Hospital had PK samples measured by liquid chromatography – mass spectrometry (MS) / MS . Multiple PK models were fit utilizing Pmetrics for R. Model covariates considered included: age, total body weight, creatinine clearance, albumin, and body mass index. PK parameters in CF patients were compared with PK parameters for 53 adults without CF who were receiving polymyxin B from the same institution. Simulations with target exposure ( area under the curve )/minimum inhibitory concentration ( MIC ) of 20 mg*L/h were conducted for different dosing schemes and MIC ranges. Main Results Nine patients with CF received between 58 and 240 mg of polymyxin B (median 1.47 mg/kg/dose [ IQR (1.43–1.65)]). A two‐compartment model adjusting polymyxin B clearance for patient Cr Cl was better than a standard two‐compartment model (p=0.004) in CF patients. When compared to PK parameters for patients without CF , PK parameters of polymyxin B in CF were similar (p>0.05). Simulations for plasma concentrations showed all regimens performed adequately at MIC s between 0.03125 and 0.125 mg/L but not at increasing MIC s of 1 and 2 mg/L. Conclusions In this pilot study of polymyxin B PK in adults with CF , the PK parameters of polymyxin B were mostly similar to adults without CF . We observed a potential association between Cr Cl and polymyxin B clearance, which stands in contrast to the general adult population. However, this observation requires further study. Additional studies focusing on optimal and safe polymyxin B dosing in CF are needed.