Oral fluconazole has variable pharmacokinetics in dogs.
bioequivalence
canine
fluconazole
formulations
pharmacokinetics
Journal
Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
Titre abrégé: J Vet Pharmacol Ther
Pays: England
ID NLM: 7910920
Informations de publication
Date de publication:
Mar 2023
Mar 2023
Historique:
revised:
23
09
2022
received:
17
08
2022
accepted:
07
10
2022
pubmed:
28
10
2022
medline:
8
3
2023
entrez:
27
10
2022
Statut:
ppublish
Résumé
The purpose of this study was to assess the effects of food and manufacturer on the oral bioavailability of fluconazole in dogs. We hypothesized feeding would decrease fluconazole bioavailability and large variability between manufacturers would occur. Six healthy purpose-bred dogs aged 2-3 years, weighing 9.5-13.7 kg, were enrolled. Each dog was administered a 100 mg fluconazole tablet from three FDA approved manufacturers (1-Glenmark, 2-Citron, 3-Harris) in a randomized crossover block study, fasted for 12 h (fasted) or 15 min after feeding (fed); each dog had 6 treatments. Blood was collected for 72 h after dosing with a 10-day washout between treatments. Fluconazole plasma concentrations were determined with mass spectrometry. Overall variability in dose-normalized drug exposure (AUC/dose) was large (range 1.9-2.9x) within each treatment, while the overall range across all treatments was 3.3-fold. The inter-dog variability in the terminal half-life was also large, 3.1-fold. The mean fed relative oral bioavailability was lower (82%-90%) compared to fasted for each formulation. Due to the large variability, the formulations were not bioequivalent. These data suggest the variability in the half-life was a major contributor to the large variability in fluconazole pharmacokinetics in dogs, while the feeding status and manufacturer were minor contributors.
Substances chimiques
Fluconazole
8VZV102JFY
Tablets
0
Types de publication
Randomized Controlled Trial, Veterinary
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
71-76Subventions
Organisme : Morris Animal Foundation
ID : D20CA-032
Informations de copyright
© 2022 John Wiley & Sons Ltd.
Références
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