Gemfibrozil (CI-719) interacts with peroxisome proliferator-activated receptors (PPARalpha) resulting in PPARalpha-mediated stimulation of fatty acid oxidation and an increase in lipoprotein lipase (LPL) synthesis. Gemfibrozil is a fibric acid derivative with hypolipidemic effects. This enhances triglyceride-rich lipoprotein clearance and reduces the expression of apolipoprotein C-III (apoC-III). The reduction in hepatic production of apoC-III result in the subsequent reduction of serum levels of very-low-density-lipoprotein cholesterol (VLDL-C). In addition, gemfibrozil-mediated PPARalpha stimulation of apoA-I and apoA-II expression results in an increase in high-density lipoprotein cholesterol (HDL-C).

2C19:24 μM(Ki), CYP2C9:5.8 μM(Ki), 2C8:69 μM(Ki), 1A2:82 μM(Ki)

Gemfibrozil对CYP3A介导的simvastatin hydroxy acid (SVA)氧化作用的抑制效果较小，但能在狗和人的肝微粒体中抑制SVA糖醛酸化作用。[1] Gemfibrozil显著抑制M-23生成，其K(i) (IC(50))值为69 (95) mM，而对M-1生成的抑制作用较弱，其K(i) (IC(50))值为273 mM。[2] Gemfibrozil强烈且竞争性地抑制CYP2C9活性，K(i) (IC(50))值为5.8 (9.6) mM。它对CYP2C19和CYP1A2活性的抑制效果较小，K(i) (IC(50))值分别为24 (47) mM和82 (136) mM。[3] Gemfibrozil是一种降脂药，能抑制在人类U373 mg星形胶质细胞和原代星形细胞中细胞因子诱导的NO产生及诱导型一氧化氮合酶(iNOS)的表达。Gemfibrozil诱导过氧化物酶体增殖体应答元素(PPRE)依赖的荧光素酶活性，该活性被人PPAR-alpha的显性负变异体DeltahPPAR-alpha的表达所抑制。Gemfibrozil强烈抑制在细胞因子刺激的星形胶质细胞中NF-kappaB、AP-1和C/EBPbeta的激活，但不抑制gamma-activation site (GAS)的激活。[4]

Gemfibrozil处理显著减少了狗在体内SVA的血浆清除率（约2-3倍）及SVA葡萄糖醛酸缀合物（及其环化产物SV）的胆汁排泄，但对SVA的一个主要氧化代谢产物的排泄无影响。[1]