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Population Pharmacokinetics of Polymyxin B
Author(s) -
Manchandani Pooja,
Thamlikitkul Visanu,
Dubrovskaya Yanina,
Babic Jessica T.,
Lye David C.,
Lee Lawrence S.,
Tam Vincent H.
Publication year - 2018
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.981
Subject(s) - polymyxin b , pharmacokinetics , volume of distribution , covariate , population , medicine , antibiotics , chromatography , chemistry , statistics , mathematics , biology , microbiology and biotechnology , environmental health
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 (V d ) using linear regression analysis. A one‐compartment model fit to the data satisfactorily (r 2 = 0.96). The best‐fit mean ± SD for clearance and V d 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.