De Cock, Pieter

de Jaeger, Annik

De Paepe, Peter

Desmet, Sarah

McWhinney, B

Vande Walle, Johan

WOLLAERT, MARGOT

English

Wollaert, Margot

Ghent University Academic Bibliography

TEICOPLANIN THERAPY IN CRITICALLY ILL CHILDREN: AN OBSERVATIONAL STUDY ON PROTEIN BINDING AND TARGET ATTAINMENTWollaert M.1,  Desmet S.1,2, McWhinney B.3, Ungerer J.3, de Jaeger A.4, Vande Walle J.5, De Paepe, P.2, De Cock P.1,2,31Department of Pharmacy, Ghent University Hospital, Ghent, Belgium; 2Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium; 3Department of Chemical Pathology, University of Queensland,Queensland, Australia; 4Department of Paediatric Intensive Care, Ghent University Hospital, Ghent, Belgium, 5Department of Nephrology, Ghent University Hospital, Ghent, BelgiumBACKGROUND and OBJECTIVES• Teicoplanin is a highly plasma proteinbound glycopeptide antibiotic.• Time-dependent bacterial killing withpersistent effects ~free(f)AUC/MIC.• Trough (Cmin) therapeutic monitoringis often used in clinical care.• Critically ill children may present withpathophysiological changes leading toaltered drug pharmacokinetics (PK)and pharmacodynamics (PD).• The objectives of this pilot study were:(a) to document teicoplanin plasmaprotein binding, and (b) to evaluatetarget attainment rates using threedifferent PK/PD targets.METHODS: study design• (f)AUC was calculated using a non-compartmental analysis based on thelog-linear trapezoidal rule withPKSolver® (MS Excel).• For first dose (f)AUC estimations, theextrapolated (f)AUC to infinity wastaken into account (max. 20%).• Correlation was assessed by means ofa scatter plot and Spearman’s RankCorrelation Coefficient using SPSS®Statistics version 24 (IBM, New York,USA).• Evaluated PK/PD targets includedAUC/MIC ≥ 750, fAUC/MIC ≥ 75(assuming a MIC of 1 mg/L) and totalCmin plasma concentration ≥ 10mg/L.2,3RESULTS• Prospective observational PK study• ICU children receiving teicoplanin• Bolus dosing regimen: 10 mg/kgevery 12 h for 3 loading doses,followed by 10 mg/kg once daily.• Blood samples were collected duringfirst and/or assumed steady-statedose intervals.METHODS: PK/PDMETHODS: bio-analysis• Free plasma concentrations wereseparated at 37 °C using a validatedultrafiltration method.1• Free and total teicoplanin plasmaconcentrations were determinedusing a validated reversed-phaseHPLC method.1• Variable PK• Plasma protein binding saturable and variable ≈ adults1• Significant underdosing• Variability in target attainmentrates : fAUC/MIC<AUC/MIC<CminCONCLUSIONSFor additional information: mail to pieter.decock@uzgent.beTable 1. Patient, treatment, sampling and PK characteristicsFigure 1 : Plasma protein bindingFigure 2: Target attainment : Cmin vs. AUC/MICFigure 3: Target attainment : AUC/MIC vs. fAUC/MICReferences : 1Roberts et al. Int J Antimicrob Agents 2014; 2Takeda et al. Clin Pharmacol 2016; 3Byrne et al. JAC 2018PATIENT CHARACTERISTICS No. (%) / Median (IQR)Gender (male/female) 15/12 (56/44)Age (years) 2.2 (0.8-4.8)Weight (kg) 12.0 (8.4-18.5)Serum albumin (g/L) 30 (27-33)Total protein (g/L) 51 (47-60)TREATMENT CHARACTERISTICS No. (%)Empirical start 17 (63)SAMPLING CHARACTERISTICS No. (%) / Median (IQR)Number of collected samples 130Collected samples per dose interval 5 (5-5)Collected total trough samples 27PK Median (IQR)AUC (mg x h/L) 823 (702-949)fAUC (mg x h/L) 72 (55-86)Cmin (mg/L) 16.0 (10.3-17.9)Intrapatient median difference betweenlowest and highest free fraction (range):4.0% (1.5-13.4%) 

Teicoplanin therapy in critically ill children : a plea for more dedicated research on optimal pharmacokinetic-pharmacodynamic indices

https://biblio.ugent.be/publication/8565473/file/8565477

Teicoplanin therapy in critically ill children : a plea for more dedicated research on optimal pharmacokinetic-pharmacodynamic indices

Abstract

Similar works

Full text

Available Versions

Ghent University Academic Bibliography