Population Pharmacokinetics of Polymyxin B.

Autor: Manchandani P; Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, Texas, USA., Thamlikitkul V; Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Dubrovskaya Y; Department of Pharmacy, New York University Langone Medical Center, New York, New York, USA., Babic JT; Department of Pharmacy, Baylor St. Luke's Medical Center, Houston, Texas, USA., Lye DC; Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Lee LS; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Tam VH; Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, Texas, USA.; Department of Pharmacy Practice and Translational Research, Houston, Texas, USA.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2018 Sep; Vol. 104 (3), pp. 534-538. Date of Electronic Publication: 2018 Jan 08.
DOI: 10.1002/cpt.981
Abstrakt: 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.
(© 2017 American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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