Population Pharmacokinetics of Polymyxin B Characterised by LC-MS/MS
Using a validated LC-MS/MS assay to measure individual polymyxin B components in 35 adult patients, this multicenter study established population pharmacokinetic parameters with a one-compartment model. Mean clearance was 2.5 L/h and volume of distribution 34.3 L. While creatinine clearance was a statistically significant covariate, its clinical impact was deemed insignificant, suggesting that renal-function-based dose adjustments may not be necessary for this last-resort antibiotic against multidrug-resistant Gram-negative infections.
The original study
Population Pharmacokinetics of Polymyxin B.
- Authors
- Manchandani P, Thamlikitkul V, Dubrovskaya Y, Babic JT, Lye DC, Lee LS, et al.
- Journal
- Clinical pharmacology and therapeutics
- Type
- Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't
- PMID
- 29238962
Original abstract
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.