PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES
Aspergillosis is a common respiratory fungal disease in African penguins (Spheniscus demersus) under managed care, and treatment failures with itraconazole due to drug resistance are increasingly common, leading to recent use of voriconazole. Empirical dosing with voriconazole based on other avian s...
Published in: | Journal of Zoo and Wildlife Medicine |
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ftbioone:10.1638/2016-0160R2.1 2023-07-30T04:02:28+02:00 PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES Michael W. Hyatt Nathan P. Wiederhold William W. Hope Katharine E. Stott Michael W. Hyatt Nathan P. Wiederhold William W. Hope Katharine E. Stott world 2017-06-01 text/HTML https://doi.org/10.1638/2016-0160R2.1 en eng American Association of Zoo Veterinarians doi:10.1638/2016-0160R2.1 All rights reserved. https://doi.org/10.1638/2016-0160R2.1 Text 2017 ftbioone https://doi.org/10.1638/2016-0160R2.1 2023-07-09T10:51:57Z Aspergillosis is a common respiratory fungal disease in African penguins (Spheniscus demersus) under managed care, and treatment failures with itraconazole due to drug resistance are increasingly common, leading to recent use of voriconazole. Empirical dosing with voriconazole based on other avian studies has resulted in adverse clinical drug effects in penguins. The objective of this study was to determine oral voriconazole pharmacokinetics (PK) in African penguins (n = 18). Single and once daily multiple oral doses of 5 mg/kg voriconazole were evaluated with a 4-mo washout period between trials. Plasma voriconazole concentrations were determined via high-performance liquid chromatography. Data was modeled using 3-compartamental population methodologies that supported first-order elimination. Observed mean peak concentration (1.89 μg/ml) after single dosing PK analysis was determined within the first hour following voriconazole administration. In the multiple-dose trial average plasma voriconazole concentrations were significantly higher on days 4 and 7 as compared with day 2. The mean estimates for volume of distribution (V/F) and clearance (Cl/F) for the multiple-dose study were 3.34 L and 0.18 L/hr, respectively. Monte Carlo simulations determined the median area under the curve (AUC0–24) at 84 hr was 37.7 μg·h/ml. As this assessment was comparable with the average AUC in humans receiving the recommended human oral dosage 200 mg b.i.d., it suggests that 5 mg/kg p.o. s.i.d. could be a safe and effective regimen in African penguins for treatment of aspergillosis. However, due to potential drug accumulation and subsequent toxicity, therapeutic drug monitoring with dosage adjustments is recommended to individualize dosing. Text Avian Studies BioOne Online Journals Journal of Zoo and Wildlife Medicine 48 2 352 362 |
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BioOne Online Journals |
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English |
description |
Aspergillosis is a common respiratory fungal disease in African penguins (Spheniscus demersus) under managed care, and treatment failures with itraconazole due to drug resistance are increasingly common, leading to recent use of voriconazole. Empirical dosing with voriconazole based on other avian studies has resulted in adverse clinical drug effects in penguins. The objective of this study was to determine oral voriconazole pharmacokinetics (PK) in African penguins (n = 18). Single and once daily multiple oral doses of 5 mg/kg voriconazole were evaluated with a 4-mo washout period between trials. Plasma voriconazole concentrations were determined via high-performance liquid chromatography. Data was modeled using 3-compartamental population methodologies that supported first-order elimination. Observed mean peak concentration (1.89 μg/ml) after single dosing PK analysis was determined within the first hour following voriconazole administration. In the multiple-dose trial average plasma voriconazole concentrations were significantly higher on days 4 and 7 as compared with day 2. The mean estimates for volume of distribution (V/F) and clearance (Cl/F) for the multiple-dose study were 3.34 L and 0.18 L/hr, respectively. Monte Carlo simulations determined the median area under the curve (AUC0–24) at 84 hr was 37.7 μg·h/ml. As this assessment was comparable with the average AUC in humans receiving the recommended human oral dosage 200 mg b.i.d., it suggests that 5 mg/kg p.o. s.i.d. could be a safe and effective regimen in African penguins for treatment of aspergillosis. However, due to potential drug accumulation and subsequent toxicity, therapeutic drug monitoring with dosage adjustments is recommended to individualize dosing. |
author2 |
Michael W. Hyatt Nathan P. Wiederhold William W. Hope Katharine E. Stott |
format |
Text |
author |
Michael W. Hyatt Nathan P. Wiederhold William W. Hope Katharine E. Stott |
spellingShingle |
Michael W. Hyatt Nathan P. Wiederhold William W. Hope Katharine E. Stott PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES |
author_facet |
Michael W. Hyatt Nathan P. Wiederhold William W. Hope Katharine E. Stott |
author_sort |
Michael W. Hyatt |
title |
PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES |
title_short |
PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES |
title_full |
PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES |
title_fullStr |
PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES |
title_full_unstemmed |
PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES |
title_sort |
pharmacokinetics of orally administered voriconazole in african penguins (spheniscus demersus) after single and multiple doses |
publisher |
American Association of Zoo Veterinarians |
publishDate |
2017 |
url |
https://doi.org/10.1638/2016-0160R2.1 |
op_coverage |
world |
genre |
Avian Studies |
genre_facet |
Avian Studies |
op_source |
https://doi.org/10.1638/2016-0160R2.1 |
op_relation |
doi:10.1638/2016-0160R2.1 |
op_rights |
All rights reserved. |
op_doi |
https://doi.org/10.1638/2016-0160R2.1 |
container_title |
Journal of Zoo and Wildlife Medicine |
container_volume |
48 |
container_issue |
2 |
container_start_page |
352 |
op_container_end_page |
362 |
_version_ |
1772813291046830080 |