| Indication |
For use as adjunctive therapy to diet to reduce elevated LDL-C,
Total-C,Triglycerides and Apo B, and to increase HDL-C in adult patients
with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson
Types IIa and IIb) |
| Pharmacodynamics |
Fenofibrate is a lipid regulating agent indicated as adjunctive
therapy to diet to reduce elevated LDL-C, Total-C,Triglycerides and Apo
B, and to increase HDL-C in adult patients with primary
hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and
IIb). Fenofibrate is also indicated as adjunctive therapy to diet for
treatment of adult patients with hypertriglyceridemia (Fredrickson Types
IV and V hyperlipidemia). Fenofibric acid, the active metabolite of
Fenofibrate, produces reductions in total cholesterol, LDL cholesterol,
apolipoprotein B, total triglycerides and triglyceride rich lipoprotein
(VLDL) in treated patients. In addition, treatment with fenofibrate
results in increases in high density lipoprotein (HDL) and apoproteins
apoAI and apoAII. |
| Mechanism of action |
Fenofibrate exerts its therapeutic effects through activation of
peroxisome proliferator activated receptor a (PPARa). This increases
lipolysis and elimination of triglyceride-rich particles from plasma by
activating lipoprotein lipase and reducing production of apoprotein
C-III. The resulting fall in triglycerides produces an alteration in the
size and composition of LDL from small, dense particles, to large
buoyant particles. These larger particles have a greater affinity for
cholesterol receptors and are catabolized rapidly. |
| Absorption |
Fenofibrate is well absorbed from the gastrointestinal tract.
After absorption, fenofibrate is mainly excreted in the urine in the
form of metabolites, primarily fenofibric acid and fenofibric acid
glucuronide |
| Volume of distribution |
- 95 L [moderate renal impairment (creatinine clearance of 50 to 90 mL/min)]
- 30 L [healthy adults]
|
| Protein binding |
~99% (Serum protein binding) |
| Metabolism |
Not Available |
| Route of elimination |
Fenofibric acid is primarily conjugated with glucuronic acid and
then excreted in urine. Following oral administration in healthy
volunteers, approximately 60% of a single dose of radiolabelled
fenofibrate appeared in urine, primarily as fenofibric acid and its
glucuronate conjugate and 25% was excreted in the feces. |
| Half life |
20 hours |
| Clearance |
|
| Toxicity |
LD50=1600 mg/kg (Oral, in mice); Investigated as a teratogen and reproductive hazard. |
