Pooja ManchandaniVisanu ThamlikitkulYanina DubrovskayaJessica T. BabicDavid C. LyeLawrence S. LeeVincent H. TamNYU Langone Medical CenterYong Loo Lin School of MedicineFaculty of Medicine, Siriraj Hospital, Mahidol UniversityUniversity of HoustonTan Tock Seng HospitalBaylor St. Luke's Medical Center2019-08-232019-08-232018-09-01Clinical Pharmacology and Therapeutics. Vol.104, No.3 (2018), 534-53815326535000992362-s2.0-85052211010https://repository.li.mahidol.ac.th/handle/20.500.14594/46417© 2017 American Society for Clinical Pharmacology and Therapeutics Polymyxin B is used as a last treatment resort for multidrug-resistant Gram-negative bacterial infections. The objectives of this study were to examine the population pharmacokinetics of polymyxin B and investigate factor(s) influencing pharmacokinetic variability. Four serial blood samples each were collected from 35 adult patients at steady state. The concentrations of individual polymyxin B components were analyzed using a validated liquid chromatography / tandem mass spectrometry assay and combined to derive total concentrations. A maximum likelihood expectation maximization approach was used to fit the data. Various demographic variables were investigated as potential covariates for clearance and volume of distribution (Vd) using linear regression analysis. A one-compartment model fit to the data satisfactorily (r2 = 0.96). The best-fit mean ± SD for clearance and Vd were 2.5 ± 1.1 L/h and 34.3 ± 16.4 L, respectively. Creatinine clearance was found to be a statistically significant covariate of clearance, but the magnitude was deemed clinically insignificant.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1002/cpt.981