Pharmacological effects of gemfibrozil on some isolated smooth muscle preparations of experimental animals

Background: Gemfibrozil is a member of fibrates (gemfibrozil, fenofibrate, ceprofibrate, and benzafibrate) which is employed for treatment of dyslipidemia particularly hypertriglyceridemiae through its action on peroxisome proliflator activated receptors (PPAR-). Objective: The aim of this work was to study the site of action and pharmacololgical effects of different doses of gemfibrozil on some isolated smooth muscles preparations of experimental animals. Materials and Methods: The experiments were conducted on isolated jejunum of rabbits, isolated spiral tracheal and urinary bladder strips of guinea pigs. Results: I- On isolated rabbit jejunum, gemfibrozil produced a dose-dependent reduction on the amplitude of jejunal contractions. The inhibitory effect of gemfibrozil was not abolished after complete blockade of alpha and beta adrenergic receptors, while it was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. On the other hand the stimulatory effects of nicotine small dose, acetylcholine, calcium gluconate, histamine and serotonin were not abolished after administration of gemfibrozil. II- On isolated tracheal spiral strips of ginea pigs, gemfibrozil produced a dose- dependent relaxation on the basal tone and a dose-dependent reduction on the amplitude of acetylcholine-induced tracheal contractions of the tracheal strips. The inhibitory effect of gemfibrozil was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. Gemfibrozil completely abolished also serotonin-induced contraction, while it has no effect on histamine or calcium-induced tracheal contractions. III- On isolated urinary bladder strips of guinea pigs, gemfibrozil produced a dose-dependent reduction on the amplitude of urinary bladder contractions. The inhibitory effect of gemfibrozil was not abolished after complete blockade of beta adrenergic receptors, while it was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. On the other hand the stimulatory effects of acetylcholine and serotonin were not abolished after administration of gemfibrozil. Conclusion: Gemfibrozil (antidyslipidemic, PPAR- agonist) reduced jejunal and urinary bladder contractions and has a relaxant effect on tracheal basal tone. So it has a beneficial effect in obstructive airway diseases and cases of urgency and frequency of micturation and urinary incontinence. However, it may be used cauciously in cases of ,GIT disturbances as constipation and prostatic hypertrophy

Associação de medicamentos: estatinas e fibratos / Combination of drugs: statins and fibrates

Monoterapia para o tratamento das dislipidemias é frequentemente insuficiente para o alcance das metas recomendadas pelas diretrizes. Entretanto, nos últimos anos, o uso de terapia combinada tem se apresentado como uma nova opção em muitos casos. Uma revisão de 36 estudos envolvendo a combinação de estatinas com fibratos apresentou 29 casos de rabdomiólise e uma prevalência geral de miopatia de 0,12 por cento. A combinação de estatinas com o genfibrozil parece causar mais rabdomiólise que com os fibratos de nova geração (especialmente quando comparado com fenofibrato ou bezafibrato). Idade avançada, diabetes, mulheres, medicações concomitantes, disfunção renal, consumo excessivo de álcool, exercícios, traumatismos e cirurgias estão também associados com maior risco de efeitos adversos.

Protective effect of coenzyme Q10 in simvastatin and gemfibrozil induced rhabdomyolysis in rats.

Administration of simvastatin (80 mg/kg, po. evening dose) and gemfibrozil (600 mg/kg, po twice) for 30 days produced significant decrease in the level of reduced glutathione, superoxide dismutase, catalase and increase in the level of lipid peroxidation and various serum parameters (creatine phosphokinase, lactate dehydrogenase, serum glutamate oxaloacetate transaminase, creatinine, urea and blood urea nitrogen). This suggested involvement of oxidative stress in rhabdomyolysis. Increase in the level of reduced glutathione, superoxide dismutase, catalase and decrease in the level of lipid peroxidation and serum parameters after administration of antioxidant CoQ10 (10 mg/kg.ip) proved the protective effect of CoQ10 in rhabdomyolysis.