Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
ATC Code: C10A B08
Pharmacotherapeutic group: Serum lipid reducing agents - fibrates.
Ciprofibrate is a new derivative of phenoxyisobutyric acid which has a marked hypolipidaemic action. It reduces both LDL and VLDL and hence the levels of triglyceride and cholesterol associated with these lipoprotein fractions. It also increases levels of HDL cholesterol. The mechanism of action of ciprofibrate is not entirely clear. It includes increased VLDL catabolism, but may also be influenced by reduced synthesis of VLDL or direct effect on the LDL receptor
Ciprofibrate is effective in the treatment of hyperlipidaemia associated with high plasma concentrations of LDL and VLDL (types IIa, IIb, III and IV according to the Fredrickson Classification). In clinical studies ciprofibrate has been shown to be effective in complementing the dietary treatment of such conditions.
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.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties

Absorption and Distribution
Ciprofibrate is readily absorbed in man, with maximum plasma concentrations occurring mainly between one and four hours following an oral dose. Following a single dose of 100mg, in volunteers, maximum plasma concentration of ciprofibrate was between 21 and 36μg/ml. In patients on chronic therapy, maximum levels from 53 to 165μg/ml have been measured. The plasma protein binding of ciprofibrate is about 98% in the therapeutic range.
Elimination
Terminal elimination half-life in patients on long term therapy varies from 38 to 86 hours.
The elimination half-life in subjects with moderate renal insufficiency was slightly increased compared with normal subjects (116.7h compared with 81.1h). In subjects with severe renal impairment, a significant increase was noted (171.9h).
Approximately 30-75% of a single dose administered to volunteers was excreted in the urine in 72 hours, either as unchanged ciprofibrate (20-25% of the total excreted) or as a conjugate. Subjects with moderate renal impairment excreted on average 7.0% of a single dose as unchanged ciprofibrate over 96 hours, compared with 6.9% in normal subjects. In subjects with severe insufficiency this was reduced to 4.7%.