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Pharmacokinetics of Repeated Oral Dosing with Coenzyme Q10 in Cavalier King Charles Spaniels with Myxomatous Mitral Valve Disease

Coenzyme Q10 (Q10) is a mitochondrial cofactor and an antioxidant with the potential to combat oxidative stress in heart failure. This study aims to determine the pharmacokinetics of repeated oral dosing of Q10 in Cavalier King Charles Spaniels (CKCS) with spontaneous myxomatous mitral valve disease...

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Autores principales: Christiansen, Liselotte B., Morsing, Malene K., Reimann, Maria Josefine, Martinussen, Torben, Birlie, Zita, Schou-Pedersen, Anne Marie V., Lykkesfeldt, Jens, Olsen, Lisbeth H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555137/
https://www.ncbi.nlm.nih.gov/pubmed/32899633
http://dx.doi.org/10.3390/antiox9090827
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author Christiansen, Liselotte B.
Morsing, Malene K.
Reimann, Maria Josefine
Martinussen, Torben
Birlie, Zita
Schou-Pedersen, Anne Marie V.
Lykkesfeldt, Jens
Olsen, Lisbeth H.
author_facet Christiansen, Liselotte B.
Morsing, Malene K.
Reimann, Maria Josefine
Martinussen, Torben
Birlie, Zita
Schou-Pedersen, Anne Marie V.
Lykkesfeldt, Jens
Olsen, Lisbeth H.
author_sort Christiansen, Liselotte B.
collection PubMed
description Coenzyme Q10 (Q10) is a mitochondrial cofactor and an antioxidant with the potential to combat oxidative stress in heart failure. This study aims to determine the pharmacokinetics of repeated oral dosing of Q10 in Cavalier King Charles Spaniels (CKCS) with spontaneous myxomatous mitral valve disease (MMVD) and to evaluate echocardiographic parameters, circulating cardiac biomarkers, and quality of life (QoL) after treatment. The study is a randomized, placebo-controlled, single-blinded crossover study. Nineteen CKCS with MMVD were randomized to receive 100 mg Q10 (ubiquinone) bi-daily for three weeks, then placebo (or in reverse order). Clinical examination, blood sampling, echocardiography, and QoL assessment were performed before and after each treatment phase. Q10 plasma concentrations were determined in plasma using a validated high-performance liquid chromatography method using electrochemical detection (HPLC-ECD). Eighteen CKCS were included in the analyses. Total plasma concentration of Q10 increased significantly (p < 0.0001) from baseline (median, 0.92 µg/mL; interquartile range (IQR), 0.70–1.26) to after treatment (median, 3.51 µg/mL; IQR, 2.30–6.88). Thirteen dogs reached the threshold of a total plasma Q10 concentration of ≥2.0 µg/mL. The average half-life (T(1/2)) of Q10 was 2.95 days (IQR, 1.75–4.02). No significant differences were observed in clinical MMVD severity, and the owner perceived QoL between Q10 and placebo treatment. The solubilized Q10 formulation was well-tolerated in the dogs. Individual variation in plasma concentrations was observed following oral treatment. A long-term placebo-controlled trial is warranted in dogs with MMVD to determine long-term efficacy on the clinical severity of MMVD.
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spelling pubmed-75551372020-10-14 Pharmacokinetics of Repeated Oral Dosing with Coenzyme Q10 in Cavalier King Charles Spaniels with Myxomatous Mitral Valve Disease Christiansen, Liselotte B. Morsing, Malene K. Reimann, Maria Josefine Martinussen, Torben Birlie, Zita Schou-Pedersen, Anne Marie V. Lykkesfeldt, Jens Olsen, Lisbeth H. Antioxidants (Basel) Article Coenzyme Q10 (Q10) is a mitochondrial cofactor and an antioxidant with the potential to combat oxidative stress in heart failure. This study aims to determine the pharmacokinetics of repeated oral dosing of Q10 in Cavalier King Charles Spaniels (CKCS) with spontaneous myxomatous mitral valve disease (MMVD) and to evaluate echocardiographic parameters, circulating cardiac biomarkers, and quality of life (QoL) after treatment. The study is a randomized, placebo-controlled, single-blinded crossover study. Nineteen CKCS with MMVD were randomized to receive 100 mg Q10 (ubiquinone) bi-daily for three weeks, then placebo (or in reverse order). Clinical examination, blood sampling, echocardiography, and QoL assessment were performed before and after each treatment phase. Q10 plasma concentrations were determined in plasma using a validated high-performance liquid chromatography method using electrochemical detection (HPLC-ECD). Eighteen CKCS were included in the analyses. Total plasma concentration of Q10 increased significantly (p < 0.0001) from baseline (median, 0.92 µg/mL; interquartile range (IQR), 0.70–1.26) to after treatment (median, 3.51 µg/mL; IQR, 2.30–6.88). Thirteen dogs reached the threshold of a total plasma Q10 concentration of ≥2.0 µg/mL. The average half-life (T(1/2)) of Q10 was 2.95 days (IQR, 1.75–4.02). No significant differences were observed in clinical MMVD severity, and the owner perceived QoL between Q10 and placebo treatment. The solubilized Q10 formulation was well-tolerated in the dogs. Individual variation in plasma concentrations was observed following oral treatment. A long-term placebo-controlled trial is warranted in dogs with MMVD to determine long-term efficacy on the clinical severity of MMVD. MDPI 2020-09-04 /pmc/articles/PMC7555137/ /pubmed/32899633 http://dx.doi.org/10.3390/antiox9090827 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Christiansen, Liselotte B.
Morsing, Malene K.
Reimann, Maria Josefine
Martinussen, Torben
Birlie, Zita
Schou-Pedersen, Anne Marie V.
Lykkesfeldt, Jens
Olsen, Lisbeth H.
Pharmacokinetics of Repeated Oral Dosing with Coenzyme Q10 in Cavalier King Charles Spaniels with Myxomatous Mitral Valve Disease
title Pharmacokinetics of Repeated Oral Dosing with Coenzyme Q10 in Cavalier King Charles Spaniels with Myxomatous Mitral Valve Disease
title_full Pharmacokinetics of Repeated Oral Dosing with Coenzyme Q10 in Cavalier King Charles Spaniels with Myxomatous Mitral Valve Disease
title_fullStr Pharmacokinetics of Repeated Oral Dosing with Coenzyme Q10 in Cavalier King Charles Spaniels with Myxomatous Mitral Valve Disease
title_full_unstemmed Pharmacokinetics of Repeated Oral Dosing with Coenzyme Q10 in Cavalier King Charles Spaniels with Myxomatous Mitral Valve Disease
title_short Pharmacokinetics of Repeated Oral Dosing with Coenzyme Q10 in Cavalier King Charles Spaniels with Myxomatous Mitral Valve Disease
title_sort pharmacokinetics of repeated oral dosing with coenzyme q10 in cavalier king charles spaniels with myxomatous mitral valve disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555137/
https://www.ncbi.nlm.nih.gov/pubmed/32899633
http://dx.doi.org/10.3390/antiox9090827
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