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Clinical pharmacokinetics and dose recommendations for posaconazole gastroresistant tablets in children with cystic fibrosis.

Bentley, S; Davies, JC; Gastine, S; Donovan, J; Standing, JF; (2021) Clinical pharmacokinetics and dose recommendations for posaconazole gastroresistant tablets in children with cystic fibrosis. The Journal of antimicrobial chemotherapy 10.1093/jac/dkab312. (In press). Green open access

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Abstract

Objectives: To investigate the population pharmacokinetics of posaconazole gastroresistant tablets in children with cystic fibrosis (CF) and perform simulations to recommend optimal doses. Patients and methods: Children from a paediatric CF centre who had received posaconazole tablets and underwent therapeutic drug monitoring were identified from pharmacy records. Relevant clinical data were collated from case notes and electronic patient records and used to develop an allometrically scaled population pharmacokinetic model. A stepwise covariate model-building exercise evaluated the influence of interacting medicines and liver function. Results: One hundred posaconazole serum concentrations were collected from 37 children with a median age of 14 years (range 7–17). Posaconazole pharmacokinetics were adequately described by a one-compartment model with inter-individual variability on clearance. Dose simulations demonstrated a 77%–83% probability of attaining a trough target of 1 mg/L with a dose of 300 mg every 12 h for two doses then 300 mg once daily (OD) in children aged 6–11 years; and 86%–88% with a dose of 400 mg every 12 h for two doses then 400 mg OD in adolescents aged 12–17 years. This dose scheme also yielded a 90% probability of achieving an AUC of 30 mg·h/L. AUC and trough concentration were highly correlated (r2 = 0.98). Simulations showed that trough concentrations of >0.75 mg/L would exceed an AUC of 30 mg·h/L in 90% of patients. Conclusions: A starting dose of 300 mg OD in those aged 6–11 years and 400 mg OD in those aged 12–17 years (following loading doses) yields a 90% probability of attaining an AUC of 30 mg·h/L.

Type: Article
Title: Clinical pharmacokinetics and dose recommendations for posaconazole gastroresistant tablets in children with cystic fibrosis.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/jac/dkab312
Publisher version: https://doi.org/10.1093/jac/dkab312
Language: English
Additional information: © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10134377
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