Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
ATC Code: C10AB02
Mechanism of Action:
Bezafibrate lowers elevated blood lipids (triglycerides and cholesterol).
Elevated VLDL and LDL are reduced by treatment with bezafibrate, whilst HDL-levels are increased. The activity of triglyceride lipases (lipoprotein lipase and hepatic lipoprotein lipase) involved in the catabolism of triglyceride-rich lipoproteins is increased by bezafibrate. In the course of the intensified degradation of triglyceride-rich lipoproteins (chylomicrons, VLDL), precursors for the formation of HDL are formed which explains an increase in HDL. Furthermore, cholesterol biosynthesis is reduced by bezafibrate, which is accompanied by a stimulation of the LDL-receptor- mediated lipoprotein catabolism.

Studies have shown bezafibrate to be effective in treating hyperlipidaemia in patients with diabetes mellitus. Some cases showed a beneficial reduction in fasting blood glucose.

Significant reductions in serum fibrinogen levels have been observed in hyperfibrinogenaemic patients treated with bezafibrate.

There is evidence that treatment with fibrates may reduce coronary heart disease events but they have not been shown to decrease all cause mortality in the primary or secondary prevention of cardiovascular disease.

Efficacy / Clinical Studies:
No data available.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
Absorption:
Bezafibrate is rapidly and almost completely absorbed from the standard film- coated tablet formulation. A peak plasma concentration of about 8mg/L is reached after 1–2 hours following a single 200mg dose in healthy volunteers.

Distribution
The protein-binding of bezafibrate in serum is approximately 95% and the apparent volume of distribution is 17 liters.

Biotransformation:
50% of the administered bezafibrate dose is recovered in the urine as unchanged drug and 20% in the form of glucuronides.

Elimination:
Elimination is rapid, with excretion almost exclusively renal. Ninety-five percent of the activity of the 14C-labelled drug is recovered in the urine and 3% in the faeces within 48 hours. 50% of the applied dose is recovered in the urine as unchanged drug and 20% in form of glucuronides. The rate of renal clearance ranges from 3.4 to 6.0L/h.
The elimination half-life of bezafibrate is 1-2 hours.
Pharmacokinetics in Special Populations:
Pharmacokinetic investigations in the elderly suggest that elimination may be delayed in cases of impaired liver function. Liver disease (except fatty liver) is a contraindication for the use of bezafibrate (see 4.3 Contraindications).
In elderly patients, there is a physiological reduction of the renal function with age. Bezafibrate dosage should be adjusted based on the serum creatinine and creatinine clearance values as indicated in the above table.
The elimination of bezafibrate is reduced in patients with impaired renal function and dosage adjustments are necessary to prevent drug accumulation and toxic effects.
Not surprisingly there is a correlation between creatinine clearance and the elimination half-life of bezafibrate; with decreasing creatinine clearance the elimination half-life is increasing.

Because of its high protein binding, bezafibrate cannot be dialysed
(cuprophane filter). The use of bezafibrate is contraindicated in dialysis patients.