Characterization and interactions between piperine and ezetimibe in their Anti-hyperlipidemic efficacy using Biopharmaceutics and Pharmacokinetics.

Abstract

Background: Piperine, a secondary metabolite, affects the antihyperlipidemic effect of Ezetimibe (EZ). Hyperlipidemia is one of the independent risk factors for cardiovascular disorders such as atherosclerosis. Antihyperlipidemic drugs are essential for reducing cardiovascular events and patient mortality. Our study aimed to improve the solubility of EZ, a lipid-lowering drug that belongs to BCS II and has low solubility. Piperine, a bioenhancer, can increase the bioavailability of other pharmaceuticals without modifying their fundamental characteristics or enhancing their efficacy. The objective of this study was to increase the bioavailability of EZ while also improving its potency and reducing its toxicity by using piperine as a bioenhancer. Therefore, rats were given piperine combined with EZ, and their antihyperlipidemic activity was assessed while fed a high-fat diet.

Method: The in vivo antihyperlipidemic effect of EZ with piperine was assessed at doses of 10 and 5-20 mg/kg b.w. The evaluation was conducted using propylthiouracil-induced and triton X-100-induced hyperlipidemia in rats. Give 400 mg/kg body weight of propylthiouracil along with piperine. Serum levels of total cholesterol (TC) (p < 0.01), triglycerides (TG) (p < 0.01), low-density lipoprotein (LDL) (p < 0.01), and very low-density lipoprotein (VLDL) (p < 0.01) all went up significantly. Additionally, it led to the induction of high-density lipoprotein (HDL) (p < 0.01). Administration of Triton X-100 via intraperitoneal injection at a single dose resulted in an elevation of lipid levels.

Results: Lower levels of high-density lipoprotein (LDL), total cholesterol (TC), triglycerides (TG), and very low-density lipoprotein (VLDL) were significantly reduced by EZ at 10 mg/kg b.w. and piperine at 20 mg/kg b.w., respectively (p < 0.01 and p < 0.05). Liver histology studies provided further evidence supporting the present findings. Areas of concentrated periportal lymphocytes and hepatocytes formed a cord pattern in rats with hyperlipidaemia. It seemed like the hepatocytes, periportal area, and centrilobular part of the liver were all normal in the group who had the treatment. An analysis of the EZ plasma drug concentration with time was carried out in a research. The medication's most effective concentration (Cmax) was determined to be within 4 h after delivery, and The quantified concentration of the active medication was detectable in the bloodstream for 24 h.

Conclusion: In combination with piperine, EZ has demonstrated significant antioxidant and antihyperlipidemic effects. This indicates that EZ could be further utilised for treating hyperlipidemia and atherosclerosis due to its potential to boost the bioavailability and oral absorption of the drug.