Development and validation of a dosing nomogram for amoxicillin in infective endocarditis
Author:
Rambaud Antoine1, Gaborit Benjamin Jean23, Deschanvres Colin2, Le Turnier Paul2, Lecomte Raphaël2, Asseray-Madani Nathalie2, Leroy Anne-Gaëlle34, Deslandes Guillaume1, Dailly Éric15, Jolliet Pascale1, Boutoille David23, Bellouard Ronan15, Gregoire Matthieu16, Raffi Francois, Boutoille David, Biron Charlotte, Lefebvre Maeva, Gaborit Benjamin Jean, Turnier Paul L E, Deschanvres Colin, Lecomte Raphael, Chauveau Marie, Asseray Nathalie, Gregoire Matthieu, Bellouard Ronan, Deslandes Guillaume, Dailly Eric, Leroy Anne-Gaëlle, Corvec Stéphane, Bemer Pascale, Caillon Jocelyne, Guillouzouic Aurélie, Huon Jean-François, Navas Dominique, Raffi Francois, Boutoille David, Biron Charlotte, Lefebvre Maeva, Gaborit Benjamin Jean, Turnier Paul L E, Deschanvres Colin, Lecomte Raphael, Chauveau Marie, Asseray Nathalie, Gregoire Matthieu, Bellouard Ronan, Deslandes Guillaume, Dailly Eric, Leroy Anne-Gaëlle, Corvec Stéphane, Bemer Pascale, Caillon Jocelyne, Guillouzouic Aurélie, Huon Jean-François, Navas Dominique,
Affiliation:
1. Clinical Pharmacology Department, CHU Nantes, Nantes, France 2. Department of Infectious Diseases, CHU Nantes and CIC 1413, INSERM, Nantes, France 3. EA 3826, Laboratory of Clinical and Experimental Therapeutics of Infections, IRS2-Nantes Biotech, University of Nantes, France 4. Department of Bacteriology, CHU Nantes, Nantes, France 5. EE 1701, MiHAR, University of Nantes, Nantes, France 6. UMR INSERM 1235, The Enteric Nervous System in Gut and Brain Disorders, University of Nantes, Nantes, France
Abstract
Abstract
Background
Amoxicillin is the first-line treatment for streptococcal or enterococcal infective endocarditis (IE) with a dose regimen adapted to weight.
Objectives
Covariates influencing pharmacokinetics (PK) of amoxicillin were identified in order to develop a dosing nomogram based on identified covariates for individual adaptation.
Patients and methods
Patients treated with amoxicillin administered by continuous infusion for IE were included retrospectively. The population PK analysis was performed using the Pmetrics package for R (NPAG algorithm). Influence of weight, ideal weight, height, BMI, body surface area, glomerular filtration rate adapted to the body surface area and calculated by the CKD-EPI method (mL/min), additional ceftriaxone treatment and serum protein level on amoxicillin PK was tested. A nomogram was then developed to determine the daily dose needed to achieve a steady-state free plasma concentration above 4× MIC, 100% of the time, without exceeding a total plasma concentration of 80 mg/L.
Results
A total of 160 patients were included. Population PK analysis was performed on 540 amoxicillin plasma concentrations. A two-compartment model best described amoxicillin PK and the glomerular filtration rate covariate significantly improved the model when included in the calculation of the elimination constant Ke.
Conclusions
This work allowed the development of a dosing nomogram that can help to increase achievement of the PK/pharmacodynamic targets in IE treated with amoxicillin.
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)
Cited by
6 articles.
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