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Fenofibric acid API Manufacturers & Suppliers

General Description:

Fenofibric acid, identified by CAS number 42017-89-0, is a notable compound with significant therapeutic applications. Fenofibric acid is a lipid-lowering agent that is used in severe hypertriglyceridemia, primary hyperlipidemia, and mixed dyslipidemia. It works to decrease elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, apolipoprotein B, while increasing high-density lipoprotein cholesterol. Due to its high hydrophilicity and poor absorption profile, prodrug ,, and other conjugated compounds of fenofibric acid, such as choline fenofibrate, have been developed for improved solubility, gastrointestinal absorption, and bioavailability, and more convenient administration.

Indications:

This drug is primarily indicated for: For use as an adjunctive therapy to diet to: (a) reduce triglyceride levels in adult patients with severe hypertriglyceridemia, and (b) reduce elevated total cholesterol, low-density-lipoprotein (LDL-C), triglycerides, and apolipoprotein B, and to increase high-density-lipoprotein (HDL-C) in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and IIb). Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Fenofibric acid undergoes metabolic processing primarily in: In vitro and in vivo metabolism studies reveal that fenofibric acid does not experience significant oxidative metabolism via the cytochrome P450 isoenzymes . The CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 enzymes are not known to play a role in the metabolism of fenofibric acid . Rather, fenofibric acid is predominantly conjugated with glucuronic acid and then excreted in urine . A small amount of fenofibric acid is reduced at the carbonyl moiety to benzhydrol metabolite which is, in turn, conjugated with glucuronic acid and excreted in urine . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Fenofibric acid are crucial for its therapeutic efficacy: Some studies have demonstrated that the bioavailability of fenofibric acid (a sample administration of 130 mg oral suspension to healthy volunteers about 4 hours after a light breakfast) is approximately 81% in the stomach, 88% in the proximal small bowel, 84% in the distal small bowel, and 78% in the colon . Nevertheless, following the oral administration of fenofibric acid in healthy volunteers, median peak plasma levels for the drug occurred about 2.5 hours after administration . Moreover, exposure after administration of three 35 mg fenofibric acid tablets is largely comparable to that of one 105 mg tablet . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Fenofibric acid is an important consideration for its dosing schedule: Following once daily dosing, fenofibric acid demonstrates an elimination associated with a half-life of about 20 hours after absorption . This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Fenofibric acid exhibits a strong affinity for binding with plasma proteins: Fenofibric acid demonstrates serum protein binding of approximately 99% in ordinary and hyperlipidemic subjects . This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Fenofibric acid from the body primarily occurs through: Fenofibric acid metabolites are largely excreted in the urine . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Fenofibric acid is distributed throughout the body with a volume of distribution of: The volume of distribution for fenofibric acid is demonstrated to be 70.9 +/- 27.5 L . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Fenofibric acid is a critical factor in determining its safe and effective dosage: In five elderly volunteers aged 77 to 87, the oral clearance of fenofibric acid after a single oral dose of fenofibrate was 1.2 L/h, which compares to 1.1 L/h in young adults . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Fenofibric acid exerts its therapeutic effects through: Various clinical studies have shown that elevated levels of total cholesterol, low-desnsity-lipoprotein (LDL-C), and apolipoprotein B (apo B) - an LDL membrane complex - are associated with human atherosclerosis . Concurrently, decreased levels of high-density-lioprotein (HDL-C) and its transport complex, apolipoproteins apo AI and apo AII, are associated with the development of atherosclerosis . Furthermore, epidemiological investigations demonstrate that cardiovascular morbidity and mortality vary directly with the levels of total cholesterol, LDL-C, and triglycerides, and inversely with the level of HDL-C . Fenofibric acid, the active metabolite of fenofibrate, subsequently produces reductions in total cholesterol, LDL-C, apo B, total triglycerides, and triglyceride rich lipoprotein (VLDL) in treated patients . Moreover, such treatment with fenofibrate also results in increases in HDL-C and apo AI and apo AII . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Fenofibric acid functions by: Having performed clinical studies with in vivo transgenic mice and in vitro human hepatocyte cultures, it is believed that the principal mechanism of action of fenofibric acid is demonstrated through its capability to activate peroxisome proliferator receptor alpha (PPAR-alpha) . By activating PPAR-alpha, fenofibric acid increases lipolysis and the elimination of triglyceride-rich particles from plasma by actuating lipoprotein lipase and reducing production of apoprotein C-III, which acts as an inhibitor of lipoprotein lipase activity . The resultant decrease in triglycerides causes an alteration in the size and composition of low-density-lipoprotein from small, dense particles to large, buoyant ones . The size of these larger low-density-lipoprotein particles have a greater affinity for cholesterol receptors and are therefore catabolized more rapidly . Additionally, fenofibric acid's activation of PPAR-alpha also induces an increase in the synthesis of apoproteins apo A-I, apo A-II, and high-density-lipoprotein . Moreover, the use of fenofibric acid can also act to reduce serum uric acid levels in ordinary or hyperuricemic individuals by increasing the urinary excretion of uric acid . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Fenofibric acid belongs to the class of organic compounds known as benzophenones. These are organic compounds containing a ketone attached to two phenyl groups, classified under the direct parent group Benzophenones. This compound is a part of the Organic compounds, falling under the Benzenoids superclass, and categorized within the Benzene and substituted derivatives class, specifically within the Benzophenones subclass.

Categories:

Fenofibric acid is categorized under the following therapeutic classes: Acids, Acyclic, Agents Causing Muscle Toxicity, Anticholesteremic Agents, Benzene Derivatives, Benzophenones, Butyrates, Drugs that are Mainly Renally Excreted, Ethers, Fibric Acids, Hypolipidemic Agents, Hypolipidemic Agents Indicated for Hyperlipidemia, Isobutyrates, Ketones, Lipid Modifying Agents, Lipid Modifying Agents, Plain, Lipid Regulating Agents, Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia, Peroxisome Proliferator Receptor alpha Agonist, Phenols, Phenyl Ethers. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.