Vol. 7, Issue 2, Part E (2025)

Hyperlipidemia, a metabolic disorder characterized by elevated plasma lipid and lipoprotein levels, is a major risk factor for cardiovascular diseases such as atherosclerosis, myocardial infarction, and stroke. Gemfibrozil, a fibrate-class hypolipidemic drug, is widely prescribed to manage hyperlipidemia by activating peroxisome proliferator-activated receptor alpha (PPAR-α) and promoting lipid catabolism. The drug is primarily metabolized through hepatic cytochrome P450 (CYP) enzymes and glucuronidation pathways. Ferulic acid, a naturally occurring phenolic compound abundant in fruits, grains, and vegetables, exhibits potent antioxidant, anti-inflammatory, and lipid-lowering properties. Given its increasing use as a dietary supplement or herbal adjuvant in metabolic disorders, the potential pharmacokinetic interaction between ferulic acid and gemfibrozil requires systematic evaluation. The present study investigated this interaction in both normal and high-fat-diet (HFD)-induced hyperlipidemic rats. Male Wistar rats (180–230 g) were divided into five groups (n = 6) and administered gemfibrozil (50 mg/kg, p.o.) alone or in combination with ferulic acid (200 mg/kg or 400 mg/kg, p.o.) as single and multiple doses. Plasma samples were collected at predetermined intervals, and gemfibrozil concentrations were quantified using a validated high-performance liquid chromatography (HPLC) method. Pharmacokinetic parameters were determined using Kinetica software (version 5.0) and analyzed statistically by one-way ANOVA followed by Dunnett’s test. Co-administration of high-dose ferulic acid (400 mg/kg) significantly reduced the maximum plasma concentration (Cmax), area under the curve (AUC₀–t), half-life (t½), and mean residence time (MRT) of gemfibrozil, with a corresponding increase in clearance (p < 0.05). These effects were more pronounced in hyperlipidemic rats, suggesting that disease-associated metabolic alterations may enhance the interaction. The findings indicate that ferulic acid modulates gemfibrozil metabolism, likely via induction of CYP enzymes or transporters, and concurrent use should be carefully monitored to avoid reduced therapeutic efficacy in hyperlipidemic patients.