Fenofibrate treatment for severe hypertriglyceridemia in dogs

Miceli, Diego Daniel; Vidal, Valérie; Blatter, M.F. Cabrera; Pignataro, Omar Pedro; Castillo, V.

doi:10.1016/j.domaniend.2020.106578

Cited by 10 publications

(37 citation statements)

References 30 publications

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“…All dogs were monitored daily throughout the study and fed a commercial canine lab chow to meet their daily metabolizable energy requirement (300 g/day divided into 0700 h and 1900 h feedings). Dogs were administered fenofibrate (Tricor®, AbbVie Inc. North Chicago, Illinois, USA) at a dose of 10 mg/kg orally once daily for 3 weeks (days 1–21) as previously described 18 . Due to the nature of the pre-post study, randomization was not performed and personnel conducting the study were not blinded.…”

Section: Methodsmentioning

confidence: 99%

Fenofibrate promotes PPARα-targeted recovery of the intestinal epithelial barrier at the host-microbe interface in dogs with diabetes mellitus

Crakes

Pires

Quach

et al. 2021

Sci Rep

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Diabetes mellitus (DM) is associated with a dysfunctional intestinal barrier and an increased risk for systemic infection and inflammation in people, though the pathogenic mechanisms leading to this are poorly understood. Using a canine model of DM, we showed that the peroxisomal proliferator-activated receptor-α agonist fenofibrate modulates plasma lipid profiles and markers of intestinal barrier function. A 3-week course of fenofibrate reduced fasting interstitial glucose and inflammatory cytokine IL-8 and TNF-α concentrations, which correlated with reduced triglyceride levels. The lipidomic profile exhibited significantly lower levels of triacylglycerols, phosphatidylethanolamines, diacylglycerols, and ceramides following fenofibrate administration. On histopathological analysis, we observed an aberrant amount of intraepithelial CD3+ T lymphocytes (IEL) in the small intestine of dogs with spontaneous and induced-DM. Fenofibrate reduced IEL density in the duodenum of dogs with DM and enhanced markers of intestinal barrier function in vivo and in vitro. There were minimal changes in the intestinal microbial composition following fenofibrate administration, suggesting that repair of intestinal barriers can be achieved independently of the resident microbiota. Our findings indicate that lipid metabolism is critical to functionality of the intestinal epithelium, which can be rescued by PPARα activation in dogs with DM.

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Section: Methodsmentioning

confidence: 99%

Fenofibrate promotes PPARα-targeted recovery of the intestinal epithelial barrier at the host-microbe interface in dogs with diabetes mellitus

Crakes

Pires

Quach

et al. 2021

Sci Rep

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show abstract

“…More recently, fenofibrate was studied in 64 dogs with primary and secondary hyperlipidemia (formulation not reported); a fenofibrate dose of 10 mg/kg orally once daily for 30 days normalized TG and CHOL in 85.9% and 53.7% of dogs, respectively. 31 The micronized, nanocrystal formulation of fenofibrate used in the present study resulted in a median reduction in TG of 81%. In the above-mentioned studies of dogs with primary and secondary hyperlipidemia, similar median decreases in TG of 84% (range, 68%-95%)…”

Section: Discussionmentioning

confidence: 71%

“…16 These elevations are likely the result of lipid vacuolar changes as described in people. 49 Serum ALP activities were not reported in previous studies on bezafibrate or fenofibrate in dogs 30,31 ; noteably, a significant reduction in ALT was reported in the bezafibrate study. 30 Conceivably, respective reductions in serum ALP and ALT activities in this and in the bezafibrate report reflect a resolving hepatic lipidosis.…”

Section: Discussionmentioning

confidence: 82%

“…In a previous study on the effect of fenofibrate in dogs with hyperlipidemia, an increase in CHOL was documented in 5 of 64 dogs. 31 The effect of fibrate drugs on CHOL in people is variable with reported paradoxical increases in LDL-C. 26 Fenofibrate was well tolerated as a treatment for hyperlipidemia in this cohort of dogs. However, given sample size, a definitive assessment of drug safety cannot be made on this study alone.…”

Section: Discussionmentioning

confidence: 85%

“…30 Fenofibrate is safe and effectual as a sole therapeutic option for management of primary and secondary hyperlipidemia in dogs but the effective dose is unknown. 31 Fenofibrate is a highly lipophilic drug with poor water solubility and oral bioavailability. 32,33 Coadministration with food is often necessary to maximize bioavailability, especially when using earlier formulations.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of a micronized, nanocrystal fenofibrate formulation in treatment of hyperlipidemia in dogs

Munro

Hulsebosch

Marks

et al. 2021

Veterinary Internal Medicne

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Background: Safe, effective, and readily available drug therapies are required for the management of hyperlipidemia and its associated complications in dogs.Objectives: To investigate the efficacy of a micronized, nanocrystal formulation of fenofibrate (Tricor) in the treatment of hyperlipidemia in dogs.Animals: Ten client-owned dogs with primary (n = 7) and secondary (n = 3) hyperlipidemia. All dogs had hypertriglyceridemia at baseline; 3 dogs also had hypercholesterolemia.Methods: Prospective dose-escalation study. Dogs were treated with fenofibrate orally once daily in up to 3 cycles of 21 days each. Fenofibrate dose was increased at the end of each cycle if hypertriglyceridemia persisted and adverse effects were not documented. Complete blood count, biochemistry, and urine protein:creatinine ratio were collected serially. Baseline (T0) parameters were compared to time of maximal reduction in serum triglyceride concentrations (T1) and reported as median (range). Results:Triglycerides normalized in all dogs (T0 = 662 mg/dL ; T1 = 113 mg/dL [81-132]; P = .002). Fenofibrate dose at T1 = 6.4 mg/kg PO q24h (range, 2.2-13.5). T1 was achieved at 3 (n = 4), 6 (n = 4), and 9 (n = 2) weeks. Serum cholesterol concentrations decreased in 9 of 10 dogs. Quiet demeanor and firm stools in 1 dog were the only reported adverse reactions. Fenofibrate administration resulted in a significant reduction in median alkaline phosphatase activity (P = .049).

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Nutritional Management of Endocrine Diseases

Fascetti,

Delaney

2023

Applied Veterinary Clinical Nutrition

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Fenofibrate treatment for severe hypertriglyceridemia in dogs

Cited by 10 publications

References 30 publications

Fenofibrate promotes PPARα-targeted recovery of the intestinal epithelial barrier at the host-microbe interface in dogs with diabetes mellitus

Fenofibrate promotes PPARα-targeted recovery of the intestinal epithelial barrier at the host-microbe interface in dogs with diabetes mellitus

Efficacy of a micronized, nanocrystal fenofibrate formulation in treatment of hyperlipidemia in dogs

Nutritional Management of Endocrine Diseases

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