Prevention and treatment research of fenofibrate for diabetic retinopathy and its clinical translation / 中华实验眼科杂志

Diabetes is a worldwide prevalent disease and diabetic retinopathy (DR) is one of the common complications, which is vision threatening and even leading to blindness.The current management of DR includes laser retina photocoagulation, vitrectomy, and frequent intravitreal anti-vascular endothelial growth factor (VEGF) agents.However, these measures do not target the root cause and their efficacy is limited.Fenofibrate is a blood lipid lowering therapeutics and its metabolite, fenofibric acid, is responsible for the pharmacology effect.Two large clinical trials (FIELD and ACCORD-Eye) have demonstrated oral fenofibrate retarded progression of DR and the needs for laser retinopexy.The animal and cell researches have revealed that fenofibric acid attenuated overexpression of basement membrane and VEGF, protected the tight junctions of endothelial cells and vascular permeability, as well as inhibited cells migration and neovascularization via suppression of inflammatory cytokines.These pharmacological effects might be materialized through several pathways, such as PPAR-α, MAPK and nuclear factor-κB (NF-кB). Blood-ocular barrier is a significant limiting factor for therapeutics reaching retina after systemic administration.Local ocular application of fenofibric acid may achieve better efficacy through improving therapeutic concentration in the eye.This drug may be delivered either by eye drop formulation or a sustained delivery device under conjunctiva or sub-Tenon.

Prevention and treatment research of fenofibrate for diabetic retinopathy and its clinical translation / 中华实验眼科杂志

Diabetes is a worldwide prevalent disease and diabetic retinopathy ( DR) is one of the common complications,which is vision threatening and even leading to blindness. The current management of DR includes laser retina photocoagulation,vitrectomy,and frequent intravitreal anti-vascular endothelial growth factor ( VEGF) agents. However,these measures do not target the root cause and their efficacy is limited. Fenofibrate is a blood lipid lowering therapeutics and its metabolite, fenofibric acid, is responsible for the pharmacology effect. Two large clinical trials ( FIELD and ACCORD-Eye) have demonstrated oral fenofibrate retarded progression of DR and the needs for laser retinopexy. The animal and cell researches have revealed that fenofibric acid attenuated overexpression of basement membrane and VEGF,protected the tight junctions of endothelial cells and vascular permeability,as well as inhibited cells migration and neovascularization via suppression of inflammatory cytokines. These pharmacological effects might be materialized through several pathways, such as PPAR-α, MAPK and nuclear factor-κB ( NF-кB ) . Blood-ocular barrier is a significant limiting factor for therapeutics reaching retina after systemic administration. Local ocular application of fenofibric acid may achieve better efficacy through improving therapeutic concentration in the eye. This drug may be delivered either by eye drop formulation or a sustained delivery device under conjunctiva or sub-Tenon.

Fenofibrate Reduces C-Reactive Protein Levels in Hypertriglyceridemic Patients With High Risks for Cardiovascular Diseases

BACKGROUND AND OBJECTIVES: The effects of fenofibrate on C-reactive protein (CRP) are under debate. We investigated the effect of fenofibrate on CRP levels and the variables determining changes. SUBJECTS AND METHODS: This case-control study enrolled 280 hypertriglyceridemic patients who were managed either with 200 mg of fenofibrate (Fenofibrate group, n=140) or with standard treatment (comparison group, n=140). CRP levels were measured before and after management for 2 months. RESULTS: CRP levels decreased in both the fenofibrate (p=0.003) and comparison (p=0.048) groups. Changes in CRP levels were not significantly different between the two groups (p=0.27) and were negatively associated with baseline CRP levels (r=-0.47, p or =1 mg/L, CRP levels also decreased in both groups (p=0.000 and p=0.001 respectively), however, more in the fenofibrate group than in the comparison group (p=0.025). The reduction of CRP was associated with higher baseline CRP levels (r=-0.29, p=0.001), lower body mass index (BMI, r=0.23, p=0.007), and fenofibrate therapy (r=0.19, p=0.025). CRP levels decreased more in the fenofibrate group than in the comparison group in patients with a BMI < or =26 kg/m2 with borderline significance (-1.21+/-1.82 mg/L vs. -0.89+/-1.92 mg/L, p=0.097). In patients with a high density lipoprotein-cholesterol level <40 mg/dL, CRP levels were reduced only in the fenofibrate group (p=0.006). CONCLUSION: Fenofibrate reduced CRP levels in hypertriglyceridemic patients with high CRP and/or low high density lipoprotein-cholesterol levels and without severe overweight. This finding suggests that fenofibrate may have an anti-inflammatory effect in selected patients.

Bioequivalence of Domestic and Imported Fenofibrate Capsules in Healthy Volunteers / 中国药房

OBJECTIVE: To evaluate the bioequivalence of domestic and imported Fenofibrate capsules in healthy volunteers. METHODS: In double-period crossover study, 18 healthy volunteers received a single oral dose of domestic Fenofibrate capsule 200 mg (test capsule) and imported capsule 200 mg (reference capsule). The content of fenofibric acid in plasma was measured with HPLC. BECS pharmacokinetics program was used to calculate the pharmacokinetic parameters and bioavailability and to evaluate the bioequivalence of two preparations. RESULTS: The main pharmacokinetic parameters of domestic Fenofibrate capsule vs. imported Fenofibrate capsule were as follows: t1/2(21.34?3.31) h vs.(21.83?4.35) h, Cmax(7.31?2.65) mg?L-1 vs. (7.28?2.66) mg?L-1, tmax(4.72?0.57) h vs.(4.67?0.59) h, AUC0～72(170.09?54.06) mg?h?L-1 vs. (172.2?54.64) mg?h?L-1, AUC0～∞(188.56?55.27) mg?h?L-1 vs. (192.27?56.62) mg?h?L-1. The relative bioavailability F0～72 and F0～∞ of domestic Fenofibrate capsule were(98.87?6.76)% vs.(98.00?6.72)%, respectively. Non-parameter test of tmax and variance analysis and t-test of Cmax and AUC0～72 showed there was no statistical difference between 2 kinds of Fenofibrate capsules. The 90% confidential intervals of AUC0～72 and Cmax of test capsule were 83.3%～116.9% and 81.1%～124.4%, respectively. CONCLUSION: The domestic and imported Fenofibrate capsules are bioequivalent.

Effect of fenofibrate on C-reactive protein levels in hypertriglyceridemic patients / 대한내과학회지

BACKGROUND: High levels of C-reactive protein (CRP) are associated with an increased risk for cardiovascular diseases. Most reports on the effect of fibrate on CRP level have inadequate study designs and the results are inconsistent. This study was designed to evaluate the effect of fenofibrate on CRP levels in hypertriglyceridemic patients. METHODS: Patients with triglyceride (TG) level over 200 mg/dL were treated with 200 mg of fenofibrate (Fenofibrate group, n=30) or with general measures (Control group, n=30). Patients with CRP levels >10 mg/L were excluded. Patients with hypercholesterolemia were treated with HMG CoA reductase inhibitor (Statin group, n=30). Lipid and lipoprotein levels were measured before and 2 months after medication. RESULTS: Baseline characteristics were similar in Fenofibrate and Control groups. Baseline CRP levels were independently associated with the presence of diabetes mellitus. Fenofibrate therapy did not change CRP levels (1.67+/-1.60 vs 1.76+/-1.88 mg/L, p=0.79) as did Control group (p=0.46). When both Fenofibrate and Control groups were divided into three subgroups in terms of baseline CRP levels, CRP levels were increased in the lowest group (p=0.019), did not change in the middle and the highest groups (p=0.89 and p=0.47 respectively). In patients with baseline CRP level > or =3 mg/L, CRP levels were decreased (p=0.041). Changes of CRP levels were independently associated with baseline CRP levels. Statin therapy decreased CRP levels (p=0.046). CONCLUSIONS: Fenofibrate did not change CRP levels in hypertriglyceridemic patients. Cardioprotective effects of fibrates may not be associated with anti-inflammatory mechanisms in contrast to those of statins.

Effect of Fibrate on Lipoprotein(a) Level in Hypertriglyceridemic Patients

BACKGROUND AND OBJECTIVES: The responses of lipoprotein (a) [Lp(a)] to lipid-lowering drugs are different from those of other lipids and lipoproteins. Most reports on the effect of fibrate on the Lp (a) level have only a few cases, with inconsistent results. This study was designed to evaluate the effect of fibrate on the Lp (a) level in hypertriglyceridemic patients. SUBJECTS AND METHODS: Patients with either a triglyceride (TG) level over 300mg/dL or TG level over 200mg/dL and a high density lipoprotein cholesterol level below 40mg/dL, were enrolled. They were treated with either fibrate (Fibrate group, n=29) or general measures (Control group, n=29). Gender and age matched patients with hypercholeste-rolemia were adopted and treated with statin (Statin group, n=29). The lipid and lipoprotein levels were measured before and after the medication for 2 months. RESULTS: The baseline Lp (a) levels were similar between the Fibrate and Control groups (p=0.19). Fibrate therapy increased the Lp (a) level from 10.3+/-16.4 to 15.1+/-15.2 mg/dL (p=0.003), but there were no changes in the Lp (a) levels in the Statin and Control groups. Before the treatment, the Lp (a) levels were negatively associated with the TG levels (r=-0.36, p=0.001). The relationship became weaker and insignificant after the medication. The more the TG level was decreased, the more the Lp (a) level was increased in all of the cases (r=-0.35, p=0.001 ) as well as in the Fibrate group (r=-0.46, p=0.013). CONCLUSION: Fibrate increased the Lp (a) level, and this elevation was associated with the reduction in the TG level. This finding might be related with a lesser cardioprotective effect of fibrate than that of statin in addition to the effect on the cholesterol level.