Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy.

Détails

ID Serval
serval:BIB_C28D55C25474
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy.
Périodique
Antimicrobial agents and chemotherapy
Auteur(s)
Leuppi-Taegtmeyer A.B., Decosterd L., Osthoff M., Mueller N.J., Buclin T., Corti N.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Statut éditorial
Publié
Date de publication
02/2019
Peer-reviewed
Oui
Volume
63
Numéro
2
Langue
anglais
Notes
Publication types: Clinical Trial, Phase IV ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Intravenous colistimethate sodium (CMS) is used to treat infections with multiresistant Gram-negative bacteria. Optimal dosing in patients undergoing continuous renal replacement therapy (CRRT) is unclear. In a prospective study, we determined CMS and colistin pharmacokinetics in 10 critically ill patients requiring CRRT (8 underwent continuous venovenous hemodialysis [CVVHD]; median blood flow, 100 ml/min). Intensive sampling was performed on treatment days 1, 3, and 5 after an intravenous CMS loading dose of 9 million international units (MU) (6 MU if body weight was <60 kg) with a consecutive 3-MU (respectively, 2 MU) maintenance dose at 8 h. CMS and colistin concentrations were determined by liquid chromatography with mass spectroscopy. A model-based population pharmacokinetic analysis incorporating CRRT settings was applied to the observations. Sequential model building indicated a monocompartmental distribution for both CMS and colistin, with interindividual variability in both volume and clearance. Hematocrit was shown to affect the efficacy of drug transfer across the filter. CRRT clearance accounted for, on average, 41% of total CMS and 28% of total colistin clearance, confirming enhanced elimination of colistin compared to normal renal function. Target colistin steady-state trough concentrations of at least 2.5 mg/liter were achieved in all patients receiving 3 MU at 8 h. In conclusion, a loading dose of 9 MU followed after 8 h by a maintenance dose of 3 MU every 8 h independent of body weight is expected to achieve therapeutic colistin concentrations in patients undergoing CVVHD using low blood flows. Colistin therapeutic drug monitoring might help to further ensure optimal dosing in individual patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02081560.).
Mots-clé
Adult, Aged, Anti-Bacterial Agents/pharmacokinetics, Anti-Bacterial Agents/therapeutic use, Chromatography, Liquid, Colistin/analogs & derivatives, Colistin/pharmacokinetics, Colistin/therapeutic use, Continuous Renal Replacement Therapy/methods, Escherichia coli/drug effects, Escherichia coli Infections/drug therapy, Escherichia coli Infections/mortality, Female, Humans, Male, Mass Spectrometry, Middle Aged, Prospective Studies, Pseudomonas Infections/drug therapy, Pseudomonas Infections/mortality, Pseudomonas aeruginosa/drug effects, colistimethate sodim, colistin, continuous renal replacement therapy, hemodiafiltration, population pharmacokinetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
04/01/2019 14:15
Dernière modification de la notice
07/02/2020 6:19
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