tricor 45 mg
A randomized, double-blind, placebo-controlled study was undertaken in 20 hypertriglyceridemic men [plasma triglyceride (TG), >2.3 mM] with low levels (<0.9 mM) of high-density lipoprotein cholesterol (HDL-C) to investigate the ability of micronized fenofibrate (Tricor or Lipidil; 200 mg/day) to affect atherogenic and thrombogenic plasma risk factors in the fed and fasted state. Each patient underwent (a) 4 weeks of dietary stabilization, (b) 8 weeks of treatment with fenofibrate or placebo, (c) a 5-week washout period, and (d) 8-weeks of treatment with the alternative medication. An oral fat-loading test (1 g fat/kg body weight) was carried out after both treatment periods. Before treatment, patients had a mean (+/- SD) total plasma TG of 3.31+/-0.93 mM; total C, 5.75+/-0.89 mM; HDL-C, 0.71+/-0.09 mM; and low-density lipoprotein (LDL)-C, 3.40+/-0.68 mM. Compared with placebo, fenofibrate reduced fasting TG levels by 36%, and triglyceride-rich lipoprotein (TRL, d<1.006 g/ml) -TG, and TRL-C levels by approximately 40%. In the postprandial state, fenofibrate reduced total TG, TRL-TG, TRL-C, TRL-apoC-III, and TRL-apoE levels by -35% (all values of p<0.01). Fasted and fed HDL-C and apoA-I levels were increased -10%, and total cholesterol/HDL cholesterol ratios were decreased -15% by fenofibrate. No significant differences were observed in mean LDL-C and LDL-apoB levels. A 6% increase in the LDL-C/LDL-apoB ratio during fenofibrate treatment indicated a shift to larger, more buoyant LDL particles. A small, but statistically significant (p<0.01) increase was observed in fasted and fed Lp(a) levels during fenofibrate treatment. Hemostatic parameters were not significantly affected by fenofibrate, except for a 12-15% decrease (p<0.05) in fibrinogen levels in the fasted and fed state, and a significant increase (43%; p<0.05) in fasting levels of plasminogen activator-inhibitor-1. These data demonstrate that micronized fenofibrate is highly effective, in both the fed and fasted state, in reducing TRL lipids and apolipoproteins, and in reducing plasma fibrinogen levels of men with an atherogenic lipoprotein profile.
University clinic and laboratory.
tricor drug interactions
Treatment of ARPE-19 cells with fenofibric acid significantly reduced the increment of permeability and the breakdown of the ARPE-19 cell monolayer induced by D-glucose, 25 mmol/l, and IL-1β, 10 ng/ml, in a dose-dependent manner. This effect was unrelated to changes in the content of tight junction proteins. Fenofibric acid prevented the activation of AMPK induced by IL-1β and the hyperpermeability induced by IL-1β was blocked by silencing AMPK.
This trial compares the efficacy of administering a combination of ezetimibe plus fenofibrate as an alternative to statin monotherapy for the treatment of dyslipidemia. In this randomized, unblinded crossover study, 43 patients with documented hypercholesterolemia requiring pharmacotherapy were randomized to receive six weeks of either a combination of 10 mg of ezetimibe plus 160 mg of fenofibrate (combination) or 10 mg of atorvastatin monotherapy (atorvastatin). The primary endpoint was the percentage reduction of low-density lipoprotein cholesterol (LDL-C).
tricor 6 mg
Several proprotein convertase subtilisin kexin type 9 (PCSK9) mutations lead to familial hypercholesterolemia by virtue of its role as a negative modulator of the low-density lipoprotein receptor (LDLr). Here, we uncover that upon dietary challenge, the down-regulation of the LDLr is also a key mechanism by which PCSK9 modulates the hepatic production of apolipoprotein-B-containing lipoproteins. Thus, adenoviral-mediated overexpression of PCSK9 in 24-h fasted mice results in massive hyperlipidemia, due to a striking increase in very-low-density lipoprotein (VLDL) triglycerides and apolipoprotein B100 hepatic output. Similar studies in LDLr (-/-) mice demonstrate that PCSK9-mediated alteration of VLDL output in the fasted state requires the LDLr. This increased production of VLDL was associated with a concomitant reduction of intrahepatic lipid stores as well as a lack of down-regulation of peroxisome proliferator-activated receptor-alpha activity and target genes expression. Finally, we show that PCSK9 hepatic expression is inhibited by the hypotriglyceridemic peroxisome proliferator-activated receptor-alpha agonist fenofibrate. In summary, the negative modulation of LDLr expression by PCSK9, which decreases plasma LDL clearance, also promotes an overproduction of nascent VLDL in vivo upon fasting.
tricor 215 mg
Treatment for periods of 6 weeks each with the following consecutive treatments: CoQ10 150 mg/day, PUFA 3000 mg/day, fenofibrate 200 mg/day, PUFA 3000 mg/day + fenofibrate 200 mg/day, PUFA 3000 mg/day + CoQ10 150 mg/day, fenofibrate 200 mg/day + CoQ10 150 mg/day, and finally, fenofibrate 200 mg/day + PUFA 3000 mg/day + CoQ10 150 mg/day.
tricor and alcohol
Ezetimibe is the first lipid-lowering drug that inhibits intestinal uptake of dietary and biliary cholesterol without affecting the absorption of fat-soluble nutrients. Following oral administration, ezetimibe is rapidly absorbed and extensively metabolised (>80%) to the pharmacologically active ezetimibe-glucuronide. Total ezetimibe (sum of 'parent' ezetimibe plus ezetimibe-glucuronide) concentrations reach a maximum 1-2 hours post-administration, followed by enterohepatic recycling and slow elimination. The estimated terminal half-life of ezetimibe and ezetimibe-glucuronide is approximately 22 hours. Consistent with the elimination half-life of ezetimibe, an approximate 2-fold accumulation is observed upon repeated once-daily administration. The recommended dose of ezetimibe 10 mg/day can be administered in the morning or evening without regard to food. There are no clinically significant effects of age, sex or race on ezetimibe pharmacokinetics and no dosage adjustment is necessary in patients with mild hepatic impairment or mild-to-severe renal insufficiency. The major metabolic pathway for ezetimibe consists of glucuronidation of the 4-hydroxyphenyl group by uridine 5'-diphosphate-glucuronosyltransferase isoenzymes to form ezetimibe-glucuronide in the intestine and liver. Approximately 78% of the dose is excreted in the faeces predominantly as ezetimibe, with the balance found in the urine mainly as ezetimibe-glucuronide. Overall, ezetimibe has a favourable drug-drug interaction profile, as evidenced by the lack of clinically relevant interactions between ezetimibe and a variety of drugs commonly used in patients with hypercholesterolaemia. Ezetimibe does not have significant effects on plasma levels of HMG-CoA reductase inhibitors commonly known as statins (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin), fibric acid derivatives (gemfibrozil, fenofibrate), digoxin, glipizide, warfarin and triphasic oral contraceptives (ethinylestradiol and levonorgestrel). Concomitant administration of food, antacids, cimetidine or statins had no significant effect on ezetimibe bioavailability. Although coadministration with gemfibrozil and fenofibrate increased the bioavailability of ezetimibe, the clinical significance is thought to be minor considering the relatively flat dose-response curve of ezetimibe and the lack of dose-related increase in adverse events. In contrast, coadministration with the bile acid binding agent colestyramine significantly decreased ezetimibe oral bioavailability (based on area under the plasma concentration-time curve of total ezetimibe). Hence, ezetimibe and colestyramine should be administered several hours apart to avoid attenuating the efficacy of ezetimibe. Finally, higher ezetimibe exposures were observed in patients receiving concomitant ciclosporin, and ezetimibe caused a small but statistically significant effect on plasma levels of ciclosporin. Because treatment experience in patients receiving ciclosporin is limited, physicians are advised to exercise caution when initiating ezetimibe in the setting of ciclosporin coadministration, and to carefully monitor ciclosporin levels.
tricor 134 mg
The present work was aimed at formulating a SMEDDS (self-microemulsifying drug delivery system) of fenofibrate and evaluating its in vitro and in vivo potential. The solubility of fenofibrate was determined in various vehicles. Pseudoternary phase diagrams were used to evaluate the microemulsification existence area, and the release rate of fenofibrate was investigated using an in vitro dissolution test. SMEDDS formulations were tested for microemulsifying properties, and the resultant microemulsions were evaluated for clarity, precipitation, and particle size distribution. Formulation development and screening was done based on results obtained from phase diagrams and characteristics of resultant microemulsions. The optimized formulation for in vitro dissolution and pharmacodynamic studies was composed of Labrafac CM10 (31.5%), Tween 80 (47.3%), and polyethylene glycol 400 (12.7%). The SMEDDS formulation showed complete release in 15 minutes as compared with the plain drug, which showed a limited dissolution rate. Comparative pharmacodynamic evaluation was investigated in terms of lipid-lowering efficacy, using a Triton-induced hypercholesterolemia model in rats. The SMEDDS formulation significantly reduced serum lipid levels in phases I and II of the Triton test, as compared with plain fenofibrate. The optimized formulation was then subjected to stability studies as per International Conference on Harmonization (ICH) guidelines and was found to be stable over 12 months. Thus, the study confirmed that the SMEDDS formulation can be used as a possible alternative to traditional oral formulations of fenofibrate to improve its bioavailability.
Outpatient university-affiliated cardiology clinic.
tricor generic medication
Aim of the study was to assess effect of fenofibrate on lipid blood composition, markers of inflammation and the state of vascular wall in patients with type 2 diabetes mellitus (DB2). We randomized 73 patients with DB2 in 2 groups. Patients of group one (n = 34) in addition to hypoglycemic and lipid lowering therapy with statins received fenofibrate (145 mg/day), patients of control group (n = 38) received standard therapy. We assessed effect of selected therapy on lipids, endothelium dependent vasodilatation (EDVD) in a test with reactive hyperemia of brachial artery, intimaAmedia thickness of common carotid arteries, levels of CAreactive protein (CRP) and uric acid, parameters of stiffness of arterial wall. At the end of the study we found in the fenofibrate group significant lowering of mean levels of total cholesterol, low density lipoprotein cholesterol, CRP, uric acid. We also noted more significant elevation of EDVD, improvement of parameters of arterial wall thickness. The use of fenofibrate in a daily dose 145 mg in patients with DB2 at the background of traditional hypoglycemic, antihypertensive, and lipid lowering therapy corrects effectively lipid disturbances and normalizes function of endothelium and parameters of vascular wall stiffness. This substantially decreases risk of vascular complications of DB2.
The aim of this study was to compare the action of fenofibrate on monocyte cytokine release between patients with isolated mixed dyslipidemia and dyslipidemia coexisting with prediabetic states in relationship with its metabolic actions.We compared 96 primary mixed dyslipidemic patients and 29 age-, sex- and weight-matched control subjects with normal lipid profile. Depending on glucose metabolism, dyslipidemic patients were allocated into one of three treatment groups: isolated dyslipidemia, dyslipidemia coexisting with impaired fasting glucose (IFG) and dyslipidemia coexisting with impaired glucose tolerance (IGT). Lipid profile, fasting and 2-h post-glucose load plasma glucose levels, HOMA and monocyte release of interleukin-1beta and MCP-1 were assessed at baseline and after 30 and 90 days of micronized fenofibrate treatment (267 mg/daily). Compared to monocytes from control subjects, monocytes of dyslipidemic patients released a greater amounts of interleukin-1beta and MCP-1. MCP-1 release was higher in the IFG group than in the remaining groups of dyslipidemic patients. In all groups of dyslipidemic patients, micronized fenofibrate reduced monocyte release of interleukin-1beta and MCP-1, and this effect was stronger in prediabetic subjects. Fenofibrate treatment also decreased HOMA in IFG and IGT patients, fasting plasma glucose in IFG subjects and 2-h post-glucose load plasma glucose in IGT patients. The observed differences between the studied groups regarding fenofibrate action on glucose homeostasis and cytokine release suggest that fibrate therapy may bring particular benefits to persons with metabolic syndrome.
We investigated the effect of fenofibrate on lipoprotein(a)levels in hypertriglyceridemic patients and the parameters relating to its effect. Patients with a triglyceride level >/=300 mg/dL or with a triglyceride level >/=200 mg/dL and a high density lipoprotein cholesterol level =40 mg/dL were treated either with 200 mg of fenofibrate(Fenofibrate group, n = 56) or with general measures (Control group,n = 56). Lipid and lipoprotein levels were measured at baseline and 2 months. Baseline lipoprotein(a) levels were negatively correlated with triglyceride (r = 20.30, P = 0.001) and alanine aminotransferase levels (r = 20.24, P = 0.012). Fenofibrate therapy increased lipoprotein(a) level from 9.4 6 10.6 to 15.6 6 17.5 mg/dL (P = 0.000). The more triglyceride levels decreased, the more lipoprotein(a) levels increased in all subjects (r = 20.46, P = 0.000) and in Control (r =20.35, P = 0.008) and Fenofibrate groups (r = 20.35, P = 0.008). Fenofibrate elevated lipoprotein(a) level greater in patients with a normal liver function. When Fenofibrate group was divided into two subgroups according to the degree of percentage change in lipoprotein(a) level, change in triglyceride level and alanine aminotransferase level were independent predictors by forward logistic regression analysis. In summary, fenofibrate therapy increases lipoprotein(a) level,and this elevation is associated with change in triglyceride level and liver function.
Reported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms.
Phospholipid transfer protein (PLTP) plays an important role in the metabolism of plasma high density lipoprotein. The mouse gene encoding PLTP and its promoter region has been cloned in our laboratory. The present study was conducted to functionally analyze the transcriptional regulation of the mouse PLTP gene. The results indicated that DNA sequences between -245 and -69 were responsible for the full promoter activity and binding motifs for transcription factor Sp1 and AP-2 within this functional promoter region were synergistically essential for the basal transcription. The transcriptional activity of this gene was significantly increased by chenodeoxycholic acid and fenofibrate, suggesting that transcription factor farnesoid X-activated receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) are likely involved in the transcriptional regulation. DNA sequence analysis suggests that DNA sequences from -407 to -395 and from -393 to -381 are homologous to the recognition motifs of FXR, and those from -859 to -847 and from -309 to -297 are similar to the potential binding motif for PPAR. These findings provide a molecular basis for further investigation of the physiological function and regulation of the PLTP gene in mice.
tricor cholesterol medicine
Fish oil has been shown to reduce serum triglyceride (TG) concentrations. In HIV-infected patients on antiretroviral therapy, high TG concentrations likely contribute to increased risk of cardiovascular disease. AIDS Clinical Trials Group A5186 examined the safety and efficacy of fish oil plus fenofibrate in subjects not achieving serum TG levels < or =200 mg/dL with either agent alone.
tricor 40 mg
The prochiral carbonyl group of fenofibrate (isopropyl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methyl propionate) is reduced during its metabolism giving rise to a chiral secondary alcohol, "reduced fenofibric acid." Chiral and diastereomeric HPLC methods have been developed for the determination of its enantiomeric composition and these have been applied to the measurement of the "reduced fenofibric acid" enantiomers in urine of rats, guinea pigs, dogs, and human volunteers given [14C]fenofibrate. In the three animal species, the reduction is markedly enantioselective for the (-)-isomer, the enantiomeric ratios (-/+) being 95:5. This was not due to differences in the excretion of the enantiomers, since when racemic "reduced fenofibric acid" was given to rats it was recovered in the urine with the same enantiomeric composition as the dose form. In humans the ratio was 52:48 showing the lack of stereoselectivity of reduction in this species.
tricor generic equivalent
Baseline and year 2 renal status were examined in relation to clinical and biochemical characteristics. Outcomes included total cardiovascular disease (CVD), cardiac and non-cardiac death over 5 years.
tricor 50 mg
Combinations of statins and fibrates may be increasingly prescribed to achieve lipid goals in high-risk patients and those with other cardiovascular risk factors, such as mixed dyslipidemia. The purpose of this retrospective cohort study was to compare rates of hospitalization for specific diagnoses in a cohort of new users of statins or fibrates, using claims data from a large United States health insurer. New users of statin, fibrate, or statin-fibrate therapy from 2004 to 2007 were identified; followed for hospitalization with rhabdomyolysis, renal impairment, hepatic injury, or pancreatitis; and confirmed by medical record review. Incidence rates (IRs) were compared across categories of fibrate or statin use, with adjusted IR ratios estimated using Poisson regression. A total of 584,784 patients initiated statins or fibrates. The IR of rhabdomyolysis in statins was 3.30 per 100,000 patient-years; the adjusted IR ratio for statin-fenofibrate combinations compared to statins alone was 3.75 (95% confidence interval 1.23 to 11.40). The IRs of renal impairment and pancreatitis in statins were 108.87 per 100,000 patient-years and 45.76 per 100,000 patient-years, respectively; the adjusted IR ratios for statin-fenofibrate combinations compared to statins alone were 1.47 (95% confidence interval 1.12 to 1.93) and 2.87 (95% confidence interval 2.05 to 4.02), respectively. The IR of hepatic injury with statins was 8.57 per 100,000 patient-years, with no risk difference between exposure groups. In conclusion, the risk for rhabdomyolysis was low, although higher in patients newly treated with statin-fibrate concurrent therapy than those treated with either as monotherapy. The risk for pancreatitis was higher in patients treated with fenofibrate, whether in combination with statins or alone.
tricor 20 mg
Many patients who receive statin therapy for hyperlipidemia-such as patients with diabetes mellitus and metabolic syndrome--have residual cardiovascular risk. These patients often have dyslipidemia, including low levels of HDL cholesterol and elevated levels of triglycerides and small, dense LDL. For such patients, combination treatment with statins and fibrates is a potentially useful strategy to improve lipid and lipoprotein profiles and reduce cardiovascular risk. However, statin-fibrate combination regimens have potential adverse effects on skeletal muscle, including myopathy. To date, no large-scale, prospective, randomized, controlled trial has evaluated the safety and efficacy of statin-fibrate combination therapy; one such trial is underway but will not report data until 2010. Until then, clinicians need to consider pharmacokinetic, pharmacodynamic, metabolic, pathophysiologic and other factors that can increase the systemic exposure of statins and/or fibrates and hence heighten the risk of toxic effects on muscles, as well as data from clinical trials and recommendations of consensus panels to optimize the safety of such combination regimens. On the basis of currently available data, fenofibrate or fenofibric acid is the fibrate of choice when used in combination with a statin because each is, in theory, associated with a lower risk of myopathy than gemfibrozil.
tricor 54 mg
Permeability increased following the administration of simvastatin (by 20%; P = 0.01), atorvastatin (by 22%; P = 0.001), fenofibrate (by 16%; P = 0.02), and quinapril (by 13%; P = 0.04) like for aspirin (P < 0.001). Turbidity analysis showed that administration of any of the drugs was associated with higher maximum absorbancy, suggesting thicker fibers, and shorter fibrinolysis time (P < 0.001). Post-treatment reduction in lysis time correlated with an increase in clot porosity in all the groups (r from 0.42 to 0.61; P from 0.01 to 0.001).
tricor brand name
We performed a systematic screening among hypercholesterolaemic outpatients attending a lipid clinic. The heterozygote subjects were followed up during more than one year and, in some of them, we compared the efficiency of cholesterol-lowering drugs belonging to the different classes: fibrate and statine.
tricor 145 mg
After a 4-week washout period, dyslipidemic patients were randomized to either micronized fenofibrate (n = 64) or atorvastatin (n = 72).
Fenofibrate can reduce the degree of liver fibrosis in mice induced by CCl4. The mechanism may involve up-regulation of PPARa, inhibition of the inflammatory response, and enhancement of SOD antioxidant activity.
Before treatment, post-prandial phase was characterized by an increase in triglycerides (3.7 +/- 1 mmol/L at baseline vs. 4.2 +/- 1, 6.5 +/- 1, 6.6 +/- 2, and 5.3 +/- 2 mmol/L after 2, 4, 6, and 8 h), a decrease in FMV (4.3 +/- 2% at baseline vs. 2.8 +/- 1, 2.2 +/- 1, and 1.3 +/- 1% after 2, 4, and 6 h), and an increase in ICAM and VCAM. After fenofibrate there was a significant reduction in fasting triglycerides (3.7 +/- 1.3 vs. 2.1 +/- 0.8 mmol/L), ICAM (480 +/- 113 vs. 269 +/- 65 ng/mL) and VCAM (1821 +/- 570 vs. 1104 +/- 376 ng/mL), and an increase in FMV (4.3 +/- 2 vs. 7.1 +/- 2%). Post-prandially triglycerides increased (2.1 +/- 1 at baseline vs. 2.4 +/- 2 and 3.6 +/- 1 mmol/L after 4 and 6 h), FMV decreased (7.1 +/- 2 at baseline vs. 5.8 +/- 2, 5.5 +/- 2, 5.9 +/- 2, 6.4 +/- 2% after 2, 4, 6, and 8 h), and there was an increase of ICAM and VCAM. Before therapy post-prandial changes in FMV had an inverse correlation with the changes in triglycerides (r = -0.34; P < 0.05) and ICAM (r = -0.66; P < 0.001).
tricor 500 mg
Scopus and MEDLINE databases were searched (up to October 15, 2014) to identify RCTs investigating whether fibrates lower plasma PAI-1 concentration or activity. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential moderators on the estimated effect sizes.
Although FIELD did not show a significant benefit with fenofibrate for major coronary events (the primary outcome), there was significant reduction in total cardiovascular events (relative risk reduction [RRR] 11%, p = 0.035 vs. placebo). The clinical benefits of fenofibrate treatment were greater in patients with marked mixed dyslipidemia (elevated triglycerides >or=200 mg/dL and low plasma levels of HDL-C), features of the metabolic syndrome commonly observed in patients with type 2 diabetes, with a RRR of 27%, p = 0.005. These data are consistent with evidence from other fibrate trials showing increased treatment benefits in patients with metabolic syndrome or type 2 diabetes and mixed dyslipidemia. The FIELD study also provided promising data for microvascular benefits with fenofibrate, specifically on the need for laser treatment for diabetic retinopathy, progression of albuminuria, and prevention of diabetes-related lower-limb amputation.
In at least some patients who experience marked HDL-C decrease when given a combination of fenofibrate and rosiglitazone, this severe adverse effect is the result of a drug interaction between the 2 pharmaceutical agents and is not reproduced by the administration of either drug singly.
tricor dosage instructions
Fenofibrate, bezafibrate, and gemfibrozil reduced plasma low-density lipoprotein cholesterol levels by 22% (P =.009), 14% (P =.042), and 11% (not significant), respectively. Plasma triglyceride levels decreased significantly (24%-36%; P <.05), whereas high-density lipoprotein cholesterol levels rose nonsignificantly after treatment with the 3 fibrates. Except for a 35% increase of apolipoprotein A-I mRNA after fenofibrate administration (P <.05), none of the individual fibrates induced significant changes in the mRNAs tested, although as a group they increased the mRNA for liver carnitine palmitoyltransferase I by 40%(P =.08; marginally significant).
tricor 48mg tablets
Six asymptomatic patients with no grossly evident gait abnormality, treated by CRPSF for a posterior pelvic disruption, were included in the study (SG). A control group (CG) of six healthy volunteers was created. All participants completed the 12-Item Short Form Health Survey version 2 (SF-12v2), the Majeed Pelvic Score (MPS), and the Iowa Pelvic Score (IPS). In addition, the participants' gait was analyzed.
tricor user reviews
The prevalence of statins' pDDIs was high in our study, mostly in the therapy before admission, with only a small number of pDDIs resulting in clinical outcome.
tricor 135 mg
Diabetic retinopathy (DR) is one of the leading risk factors and causes of blindness worldwide. Tight glucose and blood pressure control has been shown to significantly decrease the risk of development as well as the progression of retinopathy and represents the cornerstone of medical management of DR. The two most threatening complications of DR are diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Photocoagulation is standard treatment for both DME and PDR. However, some patients suffer permanent visual loss despite therapy. Treatment with fibrates first showed reduction in hard exudates, an effect subsequently shown with statins in short term studies, in particular two randomized studies in patients with macular edema. In the FIELD study which pre-specified microvascular outcomes, fenofibrate reduced laser treatment for DME or PDR by 31%:164 (3.4%) patients on fenofibrate vs. 238 (4.9%) on placebo (p<0.001). In the ophthalmology sub-study of FIELD, the composite exploratory endpoint of 2-step progression of ETDRS retinopathy grade, macular edema or laser treatment was significantly reduced by 34%: 53 (11.1%) patients on fenofibrate vs. 75 (16.1%) on placebo (p=0.022). Conversely, there was no reduction in laser treatment or reduced progression of retinopathy in two large scale studies of statins where cardiovascular events were significantly reduced. Neither class of lipid-lowering drugs consistently improved visual acuity. In the ACCORD-EYE study, the combination of fenofibrate and simvastatin reduced by 40% the rate of progression of diabetic retinopathy compared with simvastatin alone. Other studies are needed to establish the place of lipid lowering drugs in the treatment of macular edema and the prevention of vision loss.
tricor generic name
Drug release from mesoporous silica systems has been widely investigated in vitro using USP Type II (paddle) dissolution apparatus. However, it is not clear if the observed enhanced in vitro dissolution can forecast drug bioavailability in vivo. In this study, the ability of different in vitro dissolution models to predict in vivo oral bioavailability in a pig model was examined. The fenofibrate-loaded mesoporous silica formulation was compared directly to a commercial reference product, Lipantil Supra®. Three in vitro dissolution methods were considered; USP Type II (paddle) apparatus, USP Type IV (flow-through cell) apparatus and a USP IV Transfer model (incorporating a SGF to FaSSIF-V2 media transfer). In silico modelling, using a physiologically based pharmacokinetic modelling and simulation software package (Gastroplus™), to generate in vitro/in vivo relationships, was also investigated. The study demonstrates that the in vitro dissolution performance of a mesoporous silica formulation varies depending on the dissolution apparatus utilised and experimental design. The findings show that the USP IV transfer model was the best predictor of in vivo bioavailability. The USP Type II (paddle) apparatus was not effective at forecasting in vivo behaviour. This observation is likely due to hydrodynamic differences between the two apparatus and the ability of the transfer model to better simulate gastrointestinal transit. The transfer model is advantageous in forecasting in vivo behaviour for formulations which promote drug supersaturation and as a result are prone to precipitation to a more energetically favourable, less soluble form. The USP IV transfer model could prove useful in future mesoporous silica formulation development. In silico modelling has the potential to assist in this process. However, further investigation is required to overcome the limitations of the model for solubility enhancing formulations.
tricor order form
Glucocorticoids (GCs) are well-known anti-inflammatory compounds, but they also inhibit cell proliferation depending on cell type. Similarly, peroxisome proliferator-activated receptors (PPARα, PPARδ, and PPARγ) also possess anti-proliferation properties beyond their canonical roles as metabolic mediators. In the present study, we investigated the potential additive or synergistic inhibitory effects on cancer cell proliferation by simultaneous application of fenofibrate and budesonide, agonists for PPARα and glucocorticoid receptor, respectively. We observed differential effects on cell proliferation in A549 and SK-MES-1 lung cancer cells by budesonide and fenofibrate. Fenofibrate inhibited cell proliferation in both TP53 wild type and deficient lung cancer cells. The anti-proliferation effect of budesonide in TP53 wild type A549 cells was abolished in SK-MES-1 cells that do not have wild type TP53 protein. An additive effect against cell proliferation by budesonide and fenofibrate combination was observed only in TP53 wild type A549 cancer cells. Analysis of cell cycle distribution and cyclin profile indicated that the inhibition of cell proliferation was associated with G1 cell cycle arrest. The suppression of NF-κB activity and ERK signaling may contribute to the inhibition of cell proliferation by budesonide and or fenofibrate. The additive inhibitory effect on cell proliferation by budesonide and fenofibrate combination suggests that the same or greater therapeutic effect could be achieved with reduced dosage and side effects when the two compounds are applied simultaneously.