Polymyxin B Pharmacokinetics in Adult Cystic Fibrosis Patients. Issue 7 (18th July 2018)

• Record Type: Journal Article
• Authors: Avedissian, Sean N.; Miglis, Cristina; Kubin, Christine J.; Rhodes, Nathaniel J.; Yin, Michael T.; Cremers, Serge; Prickett, Michelle; Scheetz, Marc H.
• Is Part Of: Pharmacotherapy. Volume 38:Issue 7(2018)
• Page Start: 730
• Page End: 738
• Publication Date: 2018-07-18
• Subjects: polymyxin B -- cystic fibrosis -- pharmacokinetics; Chemotherapy -- Periodicals; Pharmacology -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1002/phar.2129
• Languages: English
• ISSNs: 0277-0008

Abstract

Abstract : 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 CrCl 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 MICs between 0.03125 and 0.125 mg/L but not at increasing MICs 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 CrCl 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.