Fibrates: Gemfibrozil

Question 1

Gemfibrozil
MOA

Answer 1

Agonists of PPARa, fibrates increase transcription of the genes for lipoprotein lipase and apoproteins ApoA1 / ApoA5. Increase A1 increases HDL in plasma, lipoprotein reduced VLDL and TG plasma increasing FFA uptake by liver/muscle. Decrease in TG also causes a modest decrease in LDL

Question 2

Gemfibrozil
Abs/Distrb/Elim

Answer 2

Given orally, well absorbed; metabolised to glucuronide conjugates excreted via the kidney

Question 3

Gemfibrozil
Clinical use

Answer 3

Used for mixed dyslipidemia (i.e. ↑in both plasma TGs and C); also in cases with low HDL and thus
↑risk of atheroma.

Question 4

Gemfibrozil
Adverse effects

Answer 4

Myopathy & Rhabdomyolysis
-Skeletal muscle toxicity is a dose related symptom (pain, tenderness, weakness)
-Predisposing factors; age-70+, renal dysfunction, diabetes, hereditary muscle disorder
-Risk is greater if combined with statin

Hepatotoxicity
-Rare; most likely develop during first few months
-Dose related
-Aminotransferase activity measured at baseline, 1-2 mths and 6-12 mths