Cargando…
Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration
Aspergillosis is a condition causing serious morbidity and mortality in captive penguins and other bird species. It can be treated with antifungal drugs, such as voriconazole. However, the pharmacokinetics of voriconazole are variable between different animal and bird species. Therefore, the pharmac...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379668/ https://www.ncbi.nlm.nih.gov/pubmed/30175535 http://dx.doi.org/10.1111/jvp.12709 |
_version_ | 1783562693338202112 |
---|---|
author | Parsley, Ruth A. Mutlow, Adrian G. Hansted, Jacqueline Taverne, Femke J. Tell, Lisa A. Gehring, Ronette |
author_facet | Parsley, Ruth A. Mutlow, Adrian G. Hansted, Jacqueline Taverne, Femke J. Tell, Lisa A. Gehring, Ronette |
author_sort | Parsley, Ruth A. |
collection | PubMed |
description | Aspergillosis is a condition causing serious morbidity and mortality in captive penguins and other bird species. It can be treated with antifungal drugs, such as voriconazole. However, the pharmacokinetics of voriconazole are variable between different animal and bird species. Therefore, the pharmacokinetics of voriconazole were investigated in this study in Magellanic penguins. Pharmacokinetic models were constructed and applied to predict the pharmacokinetics of voriconazole during long‐term treatment in Magellanic penguins, since the voriconazole treatment duration in chronic aspergillosis cases can last up to several months. Plasma voriconazole concentration–time data from adult Magellanic penguins (Spheniscus magellanicus; n = 15) following a single oral (PO) dose of either 2.5 mg/kg or 5 mg/kg in a herring in three separate study periods 7–12 months apart were collected. Mean plasma voriconazole concentrations were above the targeted MIC for Aspergillus fumigatus for 2 hr following a single 2.5 mg/kg voriconazole dose while the plasma concentrations exceeded the MIC for least 24 hr following a 5 mg/kg dose. Nonlinear mixed‐effects modeling was used to fit two pharmacokinetic models, one with first‐order and another with saturable elimination, to the single‐dose data. Fits were good for both, as long as dose was included as a covariate for the first‐order model so that clearance was lower and the half‐life longer for animals receiving the 5 mg/kg dose. Although the single‐dose data suggested saturated elimination at higher concentrations, the model with saturable elimination did not predict plasma voriconazole concentrations well for a clinical aspergillosis case receiving long‐term treatment, possibly because of induction of metabolizing enzymes with chronic exposure. Pharmacokinetic models should accurately predict plasma drug concentrations for different dosage regimens in order to be applicable in the field. Future studies should focus on determining clearance at steady‐state to be able to refine the pharmacokinetic models presented here and improve model performance for long‐term oral voriconazole administration in Magellanic penguins. |
format | Online Article Text |
id | pubmed-7379668 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73796682020-07-27 Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration Parsley, Ruth A. Mutlow, Adrian G. Hansted, Jacqueline Taverne, Femke J. Tell, Lisa A. Gehring, Ronette J Vet Pharmacol Ther Scientific Papers Aspergillosis is a condition causing serious morbidity and mortality in captive penguins and other bird species. It can be treated with antifungal drugs, such as voriconazole. However, the pharmacokinetics of voriconazole are variable between different animal and bird species. Therefore, the pharmacokinetics of voriconazole were investigated in this study in Magellanic penguins. Pharmacokinetic models were constructed and applied to predict the pharmacokinetics of voriconazole during long‐term treatment in Magellanic penguins, since the voriconazole treatment duration in chronic aspergillosis cases can last up to several months. Plasma voriconazole concentration–time data from adult Magellanic penguins (Spheniscus magellanicus; n = 15) following a single oral (PO) dose of either 2.5 mg/kg or 5 mg/kg in a herring in three separate study periods 7–12 months apart were collected. Mean plasma voriconazole concentrations were above the targeted MIC for Aspergillus fumigatus for 2 hr following a single 2.5 mg/kg voriconazole dose while the plasma concentrations exceeded the MIC for least 24 hr following a 5 mg/kg dose. Nonlinear mixed‐effects modeling was used to fit two pharmacokinetic models, one with first‐order and another with saturable elimination, to the single‐dose data. Fits were good for both, as long as dose was included as a covariate for the first‐order model so that clearance was lower and the half‐life longer for animals receiving the 5 mg/kg dose. Although the single‐dose data suggested saturated elimination at higher concentrations, the model with saturable elimination did not predict plasma voriconazole concentrations well for a clinical aspergillosis case receiving long‐term treatment, possibly because of induction of metabolizing enzymes with chronic exposure. Pharmacokinetic models should accurately predict plasma drug concentrations for different dosage regimens in order to be applicable in the field. Future studies should focus on determining clearance at steady‐state to be able to refine the pharmacokinetic models presented here and improve model performance for long‐term oral voriconazole administration in Magellanic penguins. John Wiley and Sons Inc. 2018-09-02 2019-01 /pmc/articles/PMC7379668/ /pubmed/30175535 http://dx.doi.org/10.1111/jvp.12709 Text en © 2018 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Scientific Papers Parsley, Ruth A. Mutlow, Adrian G. Hansted, Jacqueline Taverne, Femke J. Tell, Lisa A. Gehring, Ronette Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration |
title | Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration |
title_full | Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration |
title_fullStr | Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration |
title_full_unstemmed | Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration |
title_short | Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration |
title_sort | application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration |
topic | Scientific Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379668/ https://www.ncbi.nlm.nih.gov/pubmed/30175535 http://dx.doi.org/10.1111/jvp.12709 |
work_keys_str_mv | AT parsleyrutha applicationofdifferentpharmacokineticmodelstodescribeandpredictpharmacokineticsofvoriconazoleinmagellanicpenguinsfollowingoraladministration AT mutlowadriang applicationofdifferentpharmacokineticmodelstodescribeandpredictpharmacokineticsofvoriconazoleinmagellanicpenguinsfollowingoraladministration AT hanstedjacqueline applicationofdifferentpharmacokineticmodelstodescribeandpredictpharmacokineticsofvoriconazoleinmagellanicpenguinsfollowingoraladministration AT tavernefemkej applicationofdifferentpharmacokineticmodelstodescribeandpredictpharmacokineticsofvoriconazoleinmagellanicpenguinsfollowingoraladministration AT telllisaa applicationofdifferentpharmacokineticmodelstodescribeandpredictpharmacokineticsofvoriconazoleinmagellanicpenguinsfollowingoraladministration AT gehringronette applicationofdifferentpharmacokineticmodelstodescribeandpredictpharmacokineticsofvoriconazoleinmagellanicpenguinsfollowingoraladministration |