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Lipway: Pharmacology: Pharmacodynamics: Fenofibrate is a hypolipidaemic agent of the fibrate class, which inhibits the synthesis of cholesterol and triglycerides.
Fenofibrate can lower blood cholesterol levels by 20 to 25% and blood triglyceride levels by 40 to 50%.
The decrease in the cholesterol level is due to a reduction of the low density atherogenic fractions (VLDL and LDL). It improves the distribution of plasma cholesterol by reducing the total cholesterol: HDL cholesterol ratio, which increases in atherogenic hyperlipidaemia.
A relationship has been established between hyperlipidaemia and atherosclerosis and between atherosclerosis and cardiovascular morbidity. Low HDL levels are associated with an increased risk of coronary disease. High triglyceride levels are associated with an increased vascular risk, but it has not been established that this relation is independent. Moreover, triglycerides may be involved in the process of atherogenesis and also of thrombogenesis.
Extravascular deposits of cholesterol (xanthoma tendinosum and tuberosum) may regress considerably or even disappear completely with prolonged treatment.
A Uricosuric effect has been demonstrated in hyperlipidaemic patients, with resultant mean reduction of blood uric acid of about 25%.
With fenofibrate treatment, an increase in apoproteins A1 and a decease in apoproteins B improve the apoprotein A1:apoprotein B ratio, which can be regarded as a marker of the risk of atherogenesis.
An inhibitory effect of fenofibrate on platelet aggregation has been demonstrated in animals, and subsequently in man, in the course of clinical trial, it is manifested in reduction of aggregation induced by ADP, arachidonic acid and adrenaline.
In rats treated with fenofibrate, 80% inhibition of hepatic microsomal HMG CoA activity has been observed. This phenomenon may explain the mechanism of action of fenofibrate in man.
The sustained release form makes it possible to maintain effective plasma concentrations for longer periods.
Pharmacokinetics: Absorption: The product is not found in unchanged form in the plasma. The major metabolite in the plasma is fenofibric acid. Fenofibric acid is strongly bound to plasma albumin and may displace oral anticoagulants from the protein binding sites and potentiate their anticoagulant effect.
Fenofibrate is readily absorbed from the gastrointestinal tract when taken with food; absorption may be reduced if fenofibrate is given on an empty stomach.
Plasma half-life: Fenofibrate is rapidly hydrolysed to its active metabolite fenofibric acid which is about 99% bound to plasma albumin. The plasma elimination half-life of fenofibric acid is about 20 hours.
Metabolism and excretion: The product is eliminated essentially by the urinary route: 70% in 24 hours, 88% in 6 days, when the amount excreted attains 93% (urine and faeces). Fenofibrate is excreted principally as fenofibric acid and its glucuronide derivative. It is not removed by haemodialysis.
