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Pharmacokinetics of Single‐Dose Rectal Zonisamide Administration in Normal Dogs

BACKGROUND: Few medications are available for parental administration to animals with seizures. Rectal administration of medications is often used if the animal cannot be administered oral medications. HYPOTHESIS/OBJECTIVES: To determine the pharmacokinetic differences in zonisamide when administere...

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Autores principales: Brewer, D.M., Cerda‐Gonzalez, S., Dewey, C.W., Boothe, D., Van Horne, K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895495/
https://www.ncbi.nlm.nih.gov/pubmed/25818215
http://dx.doi.org/10.1111/jvim.12540
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author Brewer, D.M.
Cerda‐Gonzalez, S.
Dewey, C.W.
Boothe, D.
Van Horne, K.
author_facet Brewer, D.M.
Cerda‐Gonzalez, S.
Dewey, C.W.
Boothe, D.
Van Horne, K.
author_sort Brewer, D.M.
collection PubMed
description BACKGROUND: Few medications are available for parental administration to animals with seizures. Rectal administration of medications is often used if the animal cannot be administered oral medications. HYPOTHESIS/OBJECTIVES: To determine the pharmacokinetic differences in zonisamide when administered rectally in either of 2 vehicles and PO to dogs. ANIMALS: Eight healthy research dogs. METHODS: Randomized cross‐over design. Zonisamide, 10 mg/kg, was administered rectally in polyethylene glycol (PEG‐R), rectally in water (H(2)O‐R), and as an oral capsule. Plasma zonisamide concentrations were measured until 72 hours after administration. Zonisamide was quantitated by HPLC and plasma concentration versus time curve data was analyzed by using noncompartmental modeling. RESULTS: Mean maximum plasma zonisamide concentrations (μg/mL) were significantly higher after oral administration (11.56 ± 4.04) compared to H(2)O‐R (5.00 ± 1.83) (P = .004). Disappearance half‐life (hours) and mean time to maximum concentration (hours) were not significantly different between methods of administration. Mean relative bioavailability of PEG‐R (85 ± 69%) was significantly higher than that of H(2)O‐R (53 ± 37%) (P = .039). Dogs tolerated all dosing forms with no evidence of adverse effects. CONCLUSIONS AND CLINICAL IMPORTANCE: The vehicle in which zonisamide is dissolved influences rectal bioavailability, with PEG preferred to H(2)O‐R. Because of the prolonged time to maximum concentration, rectal administration of zonisamide should not be used to treat status epilepticus in dogs. A dose higher than what was used in this study might be necessary, if currently recommended minimum therapeutic concentrations (10 μg/mL) are to be achieved with a single‐dose administration.
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spelling pubmed-48954952016-06-22 Pharmacokinetics of Single‐Dose Rectal Zonisamide Administration in Normal Dogs Brewer, D.M. Cerda‐Gonzalez, S. Dewey, C.W. Boothe, D. Van Horne, K. J Vet Intern Med Standard Articles BACKGROUND: Few medications are available for parental administration to animals with seizures. Rectal administration of medications is often used if the animal cannot be administered oral medications. HYPOTHESIS/OBJECTIVES: To determine the pharmacokinetic differences in zonisamide when administered rectally in either of 2 vehicles and PO to dogs. ANIMALS: Eight healthy research dogs. METHODS: Randomized cross‐over design. Zonisamide, 10 mg/kg, was administered rectally in polyethylene glycol (PEG‐R), rectally in water (H(2)O‐R), and as an oral capsule. Plasma zonisamide concentrations were measured until 72 hours after administration. Zonisamide was quantitated by HPLC and plasma concentration versus time curve data was analyzed by using noncompartmental modeling. RESULTS: Mean maximum plasma zonisamide concentrations (μg/mL) were significantly higher after oral administration (11.56 ± 4.04) compared to H(2)O‐R (5.00 ± 1.83) (P = .004). Disappearance half‐life (hours) and mean time to maximum concentration (hours) were not significantly different between methods of administration. Mean relative bioavailability of PEG‐R (85 ± 69%) was significantly higher than that of H(2)O‐R (53 ± 37%) (P = .039). Dogs tolerated all dosing forms with no evidence of adverse effects. CONCLUSIONS AND CLINICAL IMPORTANCE: The vehicle in which zonisamide is dissolved influences rectal bioavailability, with PEG preferred to H(2)O‐R. Because of the prolonged time to maximum concentration, rectal administration of zonisamide should not be used to treat status epilepticus in dogs. A dose higher than what was used in this study might be necessary, if currently recommended minimum therapeutic concentrations (10 μg/mL) are to be achieved with a single‐dose administration. John Wiley and Sons Inc. 2015-03-27 2015 /pmc/articles/PMC4895495/ /pubmed/25818215 http://dx.doi.org/10.1111/jvim.12540 Text en Copyright © 2014 by the American College of Veterinary Internal Medicine
spellingShingle Standard Articles
Brewer, D.M.
Cerda‐Gonzalez, S.
Dewey, C.W.
Boothe, D.
Van Horne, K.
Pharmacokinetics of Single‐Dose Rectal Zonisamide Administration in Normal Dogs
title Pharmacokinetics of Single‐Dose Rectal Zonisamide Administration in Normal Dogs
title_full Pharmacokinetics of Single‐Dose Rectal Zonisamide Administration in Normal Dogs
title_fullStr Pharmacokinetics of Single‐Dose Rectal Zonisamide Administration in Normal Dogs
title_full_unstemmed Pharmacokinetics of Single‐Dose Rectal Zonisamide Administration in Normal Dogs
title_short Pharmacokinetics of Single‐Dose Rectal Zonisamide Administration in Normal Dogs
title_sort pharmacokinetics of single‐dose rectal zonisamide administration in normal dogs
topic Standard Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895495/
https://www.ncbi.nlm.nih.gov/pubmed/25818215
http://dx.doi.org/10.1111/jvim.12540
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