Fibrates

Mechanism of Action

1.       Inhibit hepatic lipid synthesis.

2.    Main action seems to be stimulating activity of lipoprotein lipase and activating receptor-mediated pathway for LDL uptake to increase clearance of cholesterol from plasma.

3.       Causes:

a.       Plasma cholesterol to decline by 10 – 15%.

b.       Plasma triglyceride to decline by 20 – 30%.

c.    Rise in HDL by 10 – 35%.

Pharmacokinetics

1.    Well absorbed orally.

2.       Extensive protein binding.

3.       Excreted mainly by the kidney.

Clinical use

1.       Bezafibrate, fenofibrate, ciprofibrate, clofibrate, gemfibrozil.

2.       Drugs of choice for mixed hyperlipidaemia.

3.    Used in hypercholesterolaemia, alone or with anion exchange resins.

4.       Contraindicated where hepatic or renal function is severely impaired.

Side effects

1.    GI: increased incidence of gallstones.

2.       Musculo-skeletal: flu-like symptoms of myalgia.

3.       Increased cancer deaths.

Drug interactions

1.    The following drugs increase plasma fibrate levels:

a.       Warfarin.

b.    Oral antidiabetic agents.

2.    Due to displacement from plasma proteins.