Van den Born, D Abraham, Martson, Anne-Grete 
ORCID: 0000-0001-6478-1959, Veringa, Anette, Punt, Nieko C, Van der Werf, Tjip S, Alffenaar, Jan-Willem C, Sturkenboom, Marieke GG and Touw, Daan J
(2023)
Voriconazole exposure is influenced by inflammation: A population pharmacokinetic model.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 61 (4).
106750-.
Abstract
<h4>Background</h4>Voriconazole is an antifungal drug used for the treatment of invasive fungal infections. Due to highly variable drug exposure, therapeutic drug monitoring (TDM) has been recommended. TDM may be helpful to predict exposure accurately, but covariates, such as severe inflammation, that influence the metabolism of voriconazole have not been included in the population pharmacokinetic (popPK) models suitable for routine TDM.<h4>Objectives</h4>To investigate whether the effect of inflammation, reflected by C-reactive protein (CRP), could improve a popPK model that can be applied in clinical care.<h4>Patients and methods</h4>Data from two previous studies were included in the popPK modelling. PopPK modelling was performed using Edsim++. Different popPK models were compared using Akaike Information Criterion and goodness-of-fit plots.<h4>Results</h4>In total, 1060 voriconazole serum concentrations from 54 patients were included in this study. The final model was a one-compartment model with non-linear elimination. Only CRP was a significant covariate, and was included in the final model and found to affect the maximum rate of enzyme activity (V<sub>max</sub>). For the final popPK model, the mean volume of distribution was 145 L [coefficient of variation percentage (CV%)=61%], mean Michaelis-Menten constant was 5.7 mg/L (CV%=119%), mean V<sub>max</sub> was 86.4 mg/h (CV%=99%) and mean bioavailability was 0.83 (CV%=143%). Internal validation using bootstrapping resulted in median values close to the population parameter estimates.<h4>Conclusions</h4>This one-compartment model with non-linear elimination and CRP as a covariate described the pharmacokinetics of voriconazole adequately.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Voriconazole, Inflammation, CRP, Pharmacokinetic modelling |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 21 Apr 2023 09:12 |
| Last Modified: | 22 Jun 2023 14:15 |
| DOI: | 10.1016/j.ijantimicag.2023.106750 |
| Open Access URL: | https://doi.org/10.1016/j.ijantimicag.2023.106750 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3169830 |
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