Pharmacokinetics of voriconazole following intravenous and oral administration and body fluid concentrations of voriconazole following repeated oral administration in horses.
Abstract: To determine the pharmacokinetics of voriconazole following IV and PO administration and assess the distribution of voriconazole into body fluids following repeated PO administration in horses. Methods: 6 clinically normal adult horses. Methods: All horses received voriconazole (10 mg/kg) IV and PO (2-week interval between treatments). Plasma voriconazole concentrations were determined prior to and at intervals following administration. Subsequently, voriconazole was administered PO (3 mg/kg) twice daily for 10 days to all horses; plasma, synovial fluid, CSF, urine, and preocular tear film concentrations of voriconazole were then assessed. Results: Mean +/- SD volume of distribution at steady state was 1,604.9 +/- 406.4 mL/kg. Systemic bioavailability of voriconazole following PO administration was 95 +/- 19%; the highest plasma concentration of 6.1 +/- 1.4 microg/mL was attained at 0.6 to 2.3 hours. Mean peak plasma concentration was 2.57 microg/mL, and mean trough plasma concentration was 1.32 microg/mL. Mean plasma, CSF, synovial fluid, urine, and preocular tear film concentrations of voriconazole after long-term PO administration were 5.163 +/- 1.594 microg/mL, 2.508 +/- 1.616 microg/mL, 3.073 +/- 2.093 microg/mL, 4.422 +/- 0.8095 microg/mL, and 3.376 +/- 1.297 microg/mL, respectively. Conclusions: Results indicated that voriconazole distributed quickly and widely in the body; following a single IV dose, initial plasma concentrations were high with a steady and early decrease in plasma concentration. Absorption of voriconazole after PO administration was excellent, compared with absorption after IV administration. Voriconazole appears to be another option for the treatment of fungal infections in horses.
Publication Date: 2007-10-06 PubMed ID: 17916020DOI: 10.2460/ajvr.68.10.1115Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates how the drug voriconazole, commonly used to combat fungal infections, behaves in a horse’s body after being given intravenously (IV) or orally (PO). It also studies the distribution of this drug into different horse body fluids after long-term administration through the mouth.
Methods
- The study involves six clinically normal adult horses.
- The horses are administered voriconazole intravenously and orally fourteen days apart. The concentration of the drug in their plasma is measured at intervals after administration.
- After this, the horses are given voriconazole orally twice a day for ten days. Following this, the concentration of voriconazole in the horse’s plasma, synovial fluid (joint fluid), cerebrospinal fluid (CSF), urine, and preocular tear film is determined.
Results
- The distribution volume of voriconazole at a steady state was found to mean around 1604.9 mL/kg, which indicates that the drug is distributed widely in the horse’s body.
- The systemic bioavailability of voriconazole, which indicates how much of the orally administered drug reaches systemic circulation unchanged, was found to be 95%. This result shows that the drug is excellently absorbed when given orally as compared to intravenously.
- The mean peak plasma concentration of voriconazole was 2.57 microg/mL, which shows that the highest concentration of voriconazole in blood was achieved after its administration.
- The voriconazole was present in measurable amounts in all the body fluids tested (plasma, CSF, synovial fluid, urine, and preocular tear film), after long-term oral administration.
Conclusion
- The results indicate that voriconazole is quickly and widely distributed in the body of horses. The initial plasma concentrations are high with a consistent and early decrease in plasma concentration.
- The excellent absorption of voriconazole after oral administration suggests its potential as an effective option for treating fungal infections in horses.
Cite This Article
APA
Colitz CM, Latimer FG, Cheng H, Chan KK, Reed SM, Pennick GJ.
(2007).
Pharmacokinetics of voriconazole following intravenous and oral administration and body fluid concentrations of voriconazole following repeated oral administration in horses.
Am J Vet Res, 68(10), 1115-1121.
https://doi.org/10.2460/ajvr.68.10.1115 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
MeSH Terms
- Administration, Oral
- Animals
- Antifungal Agents / administration & dosage
- Antifungal Agents / blood
- Antifungal Agents / pharmacokinetics
- Biological Availability
- Body Fluids / physiology
- Cross-Over Studies
- Half-Life
- Horses / physiology
- Pyrimidines / administration & dosage
- Pyrimidines / blood
- Pyrimidines / pharmacokinetics
- Reference Values
- Triazoles / administration & dosage
- Triazoles / blood
- Triazoles / pharmacokinetics
- Voriconazole
Citations
This article has been cited 5 times.- Tamura N, Okano A, Kuroda T, Niwa H, Kusano K, Matsuda Y, Fukuda K, Mita H, Nagata S. Utility of systemic voriconazole in equine keratomycosis based on pharmacokinetic-pharmacodynamic analysis of tear fluid following oral administration. Vet Ophthalmol 2020 Jul;23(4):640-647.
- Whitehead AE, Whitty J, Scott M, Léguillette R. Reversible dysphagia secondary to guttural pouch mycosis in a gelding treated medically with voriconazole and surgically with carotid occlusion and esophagostomy. Can Vet J 2018 Feb;59(2):165-170.
- Felton T, Troke PF, Hope WW. Tissue penetration of antifungal agents. Clin Microbiol Rev 2014 Jan;27(1):68-88.
- Weiler S, Fiegl D, MacFarland R, Stienecke E, Bellmann-Weiler R, Dunzendorfer S, Joannidis M, Bellmann R. Human tissue distribution of voriconazole. Antimicrob Agents Chemother 2011 Feb;55(2):925-8.
- Toner S, Leguillette R, Israel J, Legge C, Samani ARE, Kavanagh M, Goodmanson M. Long-term follow-up of laryngeal Rhinosporidium seeberi diagnosed by PCR and treated with laser ablation and voriconazole nebulization in a retired thoroughbred polo horse. Can Vet J 2024 Jul;65(7):667-674.
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