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Fenofibrate
- 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)
- pharmacologypharmacology:
- mechanism: 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.
- toxicity: LD<sub>50</sub>=1600 mg/kg (Oral, in mice); Investigated as a teratogen and reproductive hazard.
- absorprion: 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
- halflife: 20 hours
- roouteelimination: 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.
- volumedistribution: * 95 L [moderate renal impairment (creatinine clearance of 50 to 90 mL/min)] * 30 L [healthy adults]
- clearance: * 1.2 L/h [Eldery]