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

Abstract

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 (T1/2) 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.

Effects of Coenzyme Q10 Supplementation on Oxidative Stress Markers, Inflammatory Markers, Lymphocyte Subpopulations, and Clinical Status in Dogs with Myxomatous Mitral Valve Disease

“…Myocardial CoQ 10 deficiency has recently been confirmed in Cavalier King Charles Spaniels with CHF due to MMVD [ 21 ], and although plasma CoQ 10 deficiency has not been confirmed in dogs with MMVD or other cardiac pathologies [ 22 , 23 ], CoQ 10 has drawn interest as a dietary supplement which could potentially positively impact the course of MMVD in dogs due to its antioxidant and other properties. In contrast to human medicine, few CoQ 10 supplementation studies have been conducted in canine cardiac patients with spontaneous disease [ 24 , 25 ], and no studies have assessed the effect of supplemental CoQ 10 on oxidative stress parameters.…”

“…To date, three studies have been conducted to assess the effects of CoQ 10 supplementation in canine cardiac patients. A few parameters were tested, and some possible benefits were detected in two of these studies [ 24 , 25 , 40 ]. An earlier study in experimental tachycardia-induced CHF showed that dogs with CHF supplemented with CoQ 10 for six weeks in total had lower filling pressures in an early stage of CHF and less hypertrophy in severe CHF when compared to non-treated dogs [ 40 ].…”

“…In the other study, the authors reported, over a period of 28 days of supplementation, an increased shortening fraction and M-mode-derived ejection fraction in a group of dogs of less than 6 kg, which could be just a consequence of a larger end-diastolic diameter [ 24 ]. The latest (single-blind, crossover) study [ 25 ] to investigate the potential benefits of CoQ 10 in canine MMVD did not show any positive effects on the severity of the disease and owner-perceived quality of life in Cavalier King Charles Spaniels supplemented with CoQ 10 for three weeks. The authors of the mentioned study concluded that a long-term placebo-controlled trial is warranted in dogs with MMVD to determine the long-term efficacy of CoQ 10 on the clinical severity of MMVD.…”

Management of Chronic Congestive Heart Failure Caused by Myxomatous Mitral Valve Disease in Dogs: A Narrative Review from 1970 to 2020

“…The research was profuse, and the drugs tested were numerous; in fact, the reviews published in these ten years regarding the therapy of CHF secondary to MMVD in dogs are 25 [ 325 , 326 , 327 , 328 , 329 , 330 , 331 , 332 , 333 , 334 , 335 , 336 , 337 , 338 , 339 , 340 , 341 , 342 , 343 , 344 , 345 , 346 , 347 , 348 , 349 ]. As in the previous decade, many studies have been published and many drugs have been tested on dogs with spontaneous disease, such as sildenafil [ 350 , 351 , 352 , 353 ], imatinib [ 354 ], atorvastatin [ 355 , 356 ], coenzyme q10 [ 357 , 358 ], amlodipine [ 359 ], BNP1–32 [ 360 ], and angiotensin receptor antagonists [ 361 ]. In this decade, several studies have been published on diuretics, with particular regard to torasemide (such as the TEST study [ 362 ] and the CARPODIEM study [ 363 ]).…”

Depleted Myocardial Coenzyme Q10 in Cavalier King Charles Spaniels with Congestive Heart Failure Due to Myxomatous Mitral Valve Disease

“…A recent multicenter, placebo-controlled clinical trial (Q-SYMBIO) including 241 human patients with CHF showed significant clinical improvements in patients receiving 300 mg of Q10 daily over two years compared to placebo [ 13 ]. Short-term (3 weeks) treatment with oral Q10 supplementation did not improve clinical parameters of MMVD severity in a cohort of CKCS in a recently published study [ 64 ]. A long-term, prospective, placebo-controlled clinical study needs to be done in dogs with MMVD and at risk of developing CHF to determine the clinical relevance of the findings in the present study.…”