Fenoflex Mechanism of Action





Full Prescribing Info
Pharmacology: Pharmacodynamics: Fenofibrate 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 fenofibrate are mediated by the activation of peroxisome proliferator activated receptor type alpha (PPARα). Through this mechanism, fenofibrate 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 LDL-cholesterol 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 HDL-cholesterol.
Fenofibric acid decreases total cholesterol (total-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), very low density lipoprotein cholesterol (VLDL-C), and triglycerides. In addition, fenofibric acid increases high density lipoprotein cholesterol (HDL-C), apolipoproteins A-I and A-II.
Fenofibrate has been shown to reduce serum uric acid concentrations in healthy and hyperuricemic individuals by increasing the urinary excretion of uric acid.
Pharmacokinetics: Fenofibrate is rapidly absorbed after oral administration. The extent of fenofibrate absorption varies between fed (60 to 90%) and fasted (30 to 50%) conditions. Food increases the rate of fenofibrate absorption by approximately 55%.
The volume of distribution of fenofibric acid is 0.89 L/kg and the active metabolite is 99% protein bound.
After oral administration, fenofibrate is rapidly hydrolyzed by esterases to the active metabolite, fenofibric acid. No unchanged fenofibrate 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 fenofibrate nor fenofibric acid undergo oxidative metabolism to a significant extent.
After absorption, fenofibrate is excreted mainly in the urine in the form of metabolites, primarily fenofibric acid and fenofibric acid glucuronide. After administration of radiolabeled fenofibrate, 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 approximately 20 hours, allowing once daily administration in a clinical setting.
The half-life of fenofibric acid is prolonged in the elderly (39 hours) and in the presence of hepatic dysfunction (45 to 57 hours). In severe renal failure, the half-life is markedly prolonged (143 hours) and during repeated administration of fenofibrate, fenofibric acid accumulates in the plasma. Dose adjustment is necessary in such patients.
Fenofibrate (Fenoflex) 160 mg capsule was shown to have comparable bioavailability to a single dose of fenofibrate 200 mg capsule in adults under fed conditions. After oral administration of a single dose fenofibrate (Fenoflex) 160 mg capsule, mean peak fenofibrate plasma concentration (Cmax) of 14.3233 ± 2.1269 mcg/mL was achieved within 4.88 ± 0.9 hours (Tmax). The area under the plasma concentration time-curve (AUC0-72h) was 178.8636 ± 53.9433 mcg·h/mL.
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