Fenobrat Actions

How long did you take this medication to work?
sponsored

Actions of Fenobrat in details

The action of the drug on the human body is called Pharmacodynamics in Medical terminology. To produce its effect and to change the pathological process that is happening the body and to reduce the symptom or cure the disease, the medicine has to function in a specific way. The changes it does to the body at cellular level gives the desired result of treating a disease. Drugs act by stimulating or inhibiting a receptor or an enzyme or a protein most of the times. Medications are produced in such a way that the ingredients target the specific site and bring about chemical changes in the body that can stop or reverse the chemical reaction which is causing the disease.
sponsored

Antihyperlipidemic.

Pharmacology: Pharmacodynamics: Fenobrat is a prodrug and has no antilipemic activity until it is hydrolyzed by tissue and plasma esterases in vivo to fenofibric acid.

The lipid modifying effects of Fenobrat are mediated by the activation of peroxisome proliferator activated receptor type alpha (PPARα). Through this mechanism, Fenobrat increases lipolysis and elimination of atherogenic triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III (an inhibitor of lipoprotein lipase activity). The reduction in triglyceride concentrations alters the size and composition of low-density lipoprotein cholesterol (LDL-C) from small, dense particles to larger, more buoyant particles that are less atherogenic and more rapidly catabolized. PPARα activation also induces an increase in the synthesis of apo A-I, A-II, and high-density lipoprotein (HDL)-cholesterol.

Fenofibric acid decreases total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), very low-density lipoprotein (VLDL)-cholesterol, and triglycerides (TG). In addition, fenofibric acid increases HDL-C, apoproteins A-I and A-II.

Fenobrat has been shown to reduce serum uric acid concentrations in healthy and hyperuricemic individuals by increasing the urinary excretion of uric acid.

Pharmacokinetics: Fenobrat is rapidly absorbed after oral administration. The extent of Fenobrat absorption is comparable between fed (60-90%) and fasted (30-50%) conditions. Food increases the rate of Fenobrat absorption by approximately 55%.

After oral administration of a 160 mg capsule (Fenobrat), to fasted adults, mean peak Fenobrat plasma concentration (14.3233±2.1269 mcg/mL) is achieved within 4.88±0.9 hrs (Tmax).

The volume of distribution of fenofibric acid is 0.89 L/kg and the active metabolite is 99% protein bound.

After oral administration, Fenobrat is rapidly hydrolyzed by esterases to the active metabolite, fenofibric acid. No unchanged Fenobrat is detected in plasma of healthy subjects after administration. Fenofibric acid is primarily conjugated with glucuronic acid and then excreted in urine. A small amount of fenofibric acid is reduced at the carbonyl moiety to a benzhydrol metabolite which is, in turn, conjugated with glucuronic acid and excreted in urine.

In vivo metabolism data indicate that neither Fenobrat nor fenofibric acid undergo oxidative metabolism to a significant extent.

After absorption, Fenobrat is excreted mainly in the urine in the form of metabolites, primarily fenofibric acid and fenofibric acid glucuronide. After administration of radiolabeled Fenobrat, approximately 60% of the dose appeared in the urine and 25% was excreted in the feces. Fenofibric acid is eliminated with a t½ of approximately 16 hrs, allowing once daily administration in a clinical setting.

The t½ of fenofibric acid is prolonged in the elderly (39 hrs) and in the presence of hepatic dysfunction (45-57 hrs). In severe renal failure, the t½ is markedly prolonged (143 hrs) and during repeated administration of Fenobrat, fenofibric acid accumulates in the plasma. Dose adjustment is necessary in such patients.

How should I take Fenobrat?

This section provides information on the proper use of a number of products that contain Fenobrat. It may not be specific to Fenobrat. Please read with care.

Use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, or do not use it for a longer time than your doctor ordered.

In addition to this medicine, your doctor may change your diet to one that is low in fat, sugar, and cholesterol. Carefully follow your doctor's order about any special diet.

This medicine is usually taken once a day. Take the medicine at the same time each day to maintain the medication's effect.

Fenoglide®, Lipofen®, Lofibra™, and Fenobrat® should be taken with a meal. Fenobrat® and Fenobrat® can be taken with or without a meal.

Swallow Fenobrat® capsules, Fenobrat® tablets, or Fenobrat® tablets whole. Do not open, crush, break, chew, or dissolve them. Do not take chipped or broken Fenobrat® tablets.

If you are also using cholestyramine, colesevelam, or colestipol, you must take Fenobrat® at least 1 hour before or 4 to 6 hours after you take these medicines.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep Fenobrat® tablets in its original container. Protect from heat, light, and moisture.

Fenobrat administration

Administration of drug is important to know because the drug absorption and action varies depending on the route and time of administration of the drug. A medicine is prescribed before meals or after meals or along with meals. The specific timing of the drug intake about food is to increase its absorption and thus its efficacy. Few work well when taken in empty stomach and few medications need to be taken 1 or 2 hrs after the meal. A drug can be in the form of a tablet, a capsule which is the oral route of administration and the same can be in IV form which is used in specific cases. Other forms of drug administration can be a suppository in anal route or an inhalation route.
sponsored

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Some brands of Fenobrat should be taken with meals to help your body better absorb the medicine. Other brands may be taken with or without food. Follow the directions on your medicine label.

Use Fenobrat regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

If you also take cholestyramine, colesevelam, colestipol: these other medicines should be taken at least 1 hour after or 4 hours before you take Fenobrat.

Fenobrat is only part of a treatment program that may also include diet, exercise, and weight control. Follow your doctor's instructions very closely.

While using Fenobrat, you may need frequent blood tests at your doctor's office. Your liver and gallbladder function may also need to be tested.

Store at room temperature away from moisture, heat, and light. Keep the tablets in their original container, along with the packet or canister of moisture-absorbing preservative.

Fenobrat pharmacology

Pharmacokinetics of a drug can be defined as what body does to the drug after it is taken. The therapeutic result of the medicine depends upon the Pharmacokinetics of the drug. It deals with the time taken for the drug to be absorbed, metabolized, the process and chemical reactions involved in metabolism and about the excretion of the drug. All these factors are essential to deciding on the efficacy of the drug. Based on these pharmacokinetic principles, the ingredients, the Pharmaceutical company decides dose and route of administration. The concentration of the drug at the site of action which is proportional to therapeutic result inside the body depends on various pharmacokinetic reactions that occur in the body.
sponsored

Mechanism of Action

The active moiety of Fenobrat is fenofibric acid. The pharmacological effects of fenofibric acid in both animals and humans have been extensively studied through oral administration of Fenobrat.

The lipid-modifying effects of fenofibric acid seen in clinical practice have been explained in vivo in transgenic mice and in vitro in human hepatocyte cultures by the activation of peroxisome proliferator activated receptor α (PPARα). Through this mechanism, Fenobrat increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III (an inhibitor of lipoprotein lipase activity).

The resulting decrease in TG produces an alteration in the size and composition of LDL from small, dense particles (which are thought to be atherogenic due to their susceptibility to oxidation), to large buoyant particles. These larger particles have a greater affinity for cholesterol receptors and are catabolized rapidly. Activation of PPARα also induces an increase in the synthesis of apolipoproteins A-I, A-II and HDL-cholesterol.

Fenobrat also reduces serum uric acid levels in hyperuricemic and normal individuals by increasing the urinary excretion of uric acid.

Pharmacodynamics

A variety of clinical studies have demonstrated that elevated levels of total-C, LDL-C, and apo B, an LDL membrane complex, are associated with human atherosclerosis. Similarly, decreased levels of HDL-C and its transport complex, apolipoprotein A (apo AI and apo AII) are associated with the development of atherosclerosis. Epidemiologic investigations have established that cardiovascular morbidity and mortality vary directly with the level of total-C, LDL-C, and TG, and inversely with the level of HDL-C. The independent effect of raising HDL-C or lowering triglycerides (TG) on the risk of cardiovascular morbidity and mortality has not been determined.

Fenofibric acid, the active metabolite of Fenobrat, produces reductions in total cholesterol, LDL cholesterol, apolipoprotein B, total triglycerides and triglyceride rich lipoprotein (VLDL) in treated patients. In addition, treatment with Fenobrat results in increases in high density lipoprotein (HDL) and apolipoproteins apoAI and apoAII.

Pharmacokinetics

Plasma concentrations of fenofibric acid after administration of three 48 mg or one 145 mg tablets are equivalent under fed conditions to one 200 mg micronized Fenobrat capsule.

Fenobrat is a pro-drug of the active chemical moiety fenofibric acid. Fenobrat is converted by ester hydrolysis in the body to fenofibric acid which is the active constituent measurable in the circulation.

Absorption

The absolute bioavailability of Fenobrat cannot be determined as the compound is virtually insoluble in aqueous media suitable for injection. However, Fenobrat is well absorbed from the gastrointestinal tract. Following oral administration in healthy volunteers, approximately 60% of a single dose of radiolabelled Fenobrat appeared in urine, primarily as fenofibric acid and its glucuronate conjugate, and 25% was excreted in the feces. Peak plasma levels of fenofibric acid occur within 6 to 8 hours after administration.

Exposure to fenofibric acid in plasma, as measured by Cmax and AUC, is not significantly different when a single 145 mg dose of Fenobrat is administered under fasting or nonfasting conditions.

Distribution

Upon multiple dosing of Fenobrat, fenofibric acid steady state is achieved within 9 days. Plasma concentrations of fenofibric acid at steady state are approximately double of those following a single dose. Serum protein binding was approximately 99% in normal and hyperlipidemic subjects.

Metabolism

Following oral administration, Fenobrat is rapidly hydrolyzed by esterases to the active metabolite, fenofibric acid; no unchanged Fenobrat is detected in plasma.

Fenofibric acid is primarily conjugated with glucuronic acid and then excreted in urine. A small amount of fenofibric acid is reduced at the carbonyl moiety to a benzhydrol metabolite which is, in turn, conjugated with glucuronic acid and excreted in urine.

In vivo metabolism data indicate that neither Fenobrat nor fenofibric acid undergo oxidative metabolism (e.g., cytochrome P450) to a significant extent.

Elimination

After absorption, Fenobrat is mainly excreted in the urine in the form of metabolites, primarily fenofibric acid and fenofibric acid glucuronide. After administration of radiolabelled Fenobrat, approximately 60% of the dose appeared in the urine and 25% was excreted in the feces.

Fenofibric acid is eliminated with a half-life of 20 hours, allowing once daily dosing.

Special Populations

Geriatrics

In elderly volunteers 77 to 87 years of age, the oral clearance of fenofibric acid following a single oral dose of Fenobrat was 1.2 L/h, which compares to 1.1 L/h in young adults. This indicates that a similar dosage regimen can be used in elderly with normal renal function, without increasing accumulation of the drug or metabolites.

Pediatrics

The pharmacokinetics of Fenobrat has not been studied in pediatric populations.

Gender

No pharmacokinetic difference between males and females has been observed for Fenobrat.

Race

The influence of race on the pharmacokinetics of Fenobrat has not been studied, however Fenobrat is not metabolized by enzymes known for exhibiting inter-ethnic variability.

Renal Impairment

The pharmacokinetics of fenofibric acid was examined in patients with mild, moderate, and severe renal impairment. Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73m2) showed 2.7-fold increase in exposure for fenofibric acid and increased accumulation of fenofibric acid during chronic dosing compared to that of healthy subjects. Patients with mild to moderate renal impairment (eGFR 30-59 mL/min/1.73m2) had similar exposure but an increase in the half-life for fenofibric acid compared to that of healthy subjects. Based on these findings, the use of Fenobrat should be avoided in patients who have severe renal impairment and dose reduction is required in patients having mild to moderate renal impairment.

Hepatic Impairment

No pharmacokinetic studies have been conducted in patients with hepatic impairment.

Drug-drug Interactions

In vitro studies using human liver microsomes indicate that Fenobrat and fenofibric acid are not inhibitors of cytochrome (CYP) P450 isoforms CYP3A4, CYP2D6, CYP2E1, or CYP1A2. They are weak inhibitors of CYP2C8, CYP2C19 and CYP2A6, and mild-to-moderate inhibitors of CYP2C9 at therapeutic concentrations.

Table 2 describes the effects of co-administered drugs on fenofibric acid systemic exposure. Table 3 describes the effects of co-administered Fenobrat or fenofibric acid on other drugs.

Table 2. Effects of Co-Administered Drugs on Fenofibric Acid Systemic Exposure from Fenobrat Administration
Co-Administered

Drug

Dosage Regimen of

Co-Administered Drug

Dosage Regimen of Fenobrat Changes in Fenofibric Acid Exposure
AUC Cmax
Lipid-lowering agents
Atorvastatin 20 mg once daily for 10 days Fenobrat 160 mg1 once daily for 10 days ↓2% ↓4%
Pravastatin 40 mg as a single dose Fenobrat 3 x 67 mg2 as a single dose ↓1% ↓2%
Fluvastatin 40 mg as a single dose Fenobrat 160 mg1 as a single dose ↓2% ↓10%
Anti-diabetic agents
Glimepiride 1 mg as a single dose Fenobrat 145 mg1 once daily for 10 days ↑1% ↓1%
Metformin 850 mg three times daily for 10 days Fenobrat 54 mg1 three times daily for 10 days ↓9% ↓6%
Rosiglitazone 8 mg once daily for 5 days Fenobrat 145 mg1 once daily for 14 days ↑10% ↑3%
1 Fenobrat (Fenobrat) oral tablet
2 Fenobrat (Fenobrat) oral micronized capsule

Table 3. Effects of Fenobrat Co-Administration on Systemic Exposure of Other Drugs
Dosage Regimen of Fenobrat Dosage Regimen of Co-Administered Drug Change in Co-Administered Drug Exposure
Analyte AUC Cmax
Lipid-lowering agents
Fenobrat 160 mg1 once daily for 10 days Atorvastatin, 20 mg once daily for 10 days Atorvastatin ↓17% 0%
Fenobrat 3 x 67 mg2 as a single dose Pravastatin, 40 mg as a single dose Pravastatin ↑13% ↑13%
3α-Hydroxyl-iso-pravastatin ↑26% ↑29%
Fenobrat 160 mg1 as a single dose Fluvastatin, 40 mg as a single dose (+)-3R, 5S-Fluvastatin ↑15% ↑16%
Anti-diabetic agents
Fenobrat 145 mg1 once daily for 10 days Glimepiride, 1 mg as a single dose Glimepiride ↑35% ↑18%
Fenobrat 54 mg1 three times daily for 10 days Metformin, 850 mg three times daily for 10 days Metformin ↑3% ↑6%
Fenobrat 145 mg1 once daily for 14 days Rosiglitazone, 8 mg once daily for 5 days Rosiglitazone ↑6% ↓1%
1 Fenobrat (Fenobrat) oral tablet
2 Fenobrat (Fenobrat) oral micronized capsule



References

  1. DailyMed. "FENOFIBRATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
  2. NCIt. "Fenofibrate: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
  3. EPA DSStox. "Fenofibrate: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).

Reviews

The results of a survey conducted on ndrugs.com for Fenobrat are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Fenobrat. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.

User reports

Consumer reported administration

No survey data has been collected yet


Consumer reviews


There are no reviews yet. Be the first to write one!


Your name: 
Email: 
Spam protection:  < Type 28 here

Information checked by Dr. Sachin Kumar, MD Pharmacology

| Privacy Policy
This site does not supply any medicines. It contains prices for information purposes only.
© 2003 - 2024 ndrugs.com All Rights Reserved