Enhanced antihyperlipidemic potential of gemfibrozil under co-administration with piperine

Gemfibrozil is a well-known potent antihyperlipidemic drug with the capacity to lower triglyceride and cholesterol levels, which are responsible for most cardiovascular and cerebrovascular diseases. In addition, gemfibrozil has a potent activity at elevating the high density lipoprotein levels. However, this drug has a very short half-life of about 2 ​h and toxicity is observed in the liver as the dose increases. The drug piperine has the capacity to enhance the bioavailability of other drugs without altering their basic properties as well as improving their activity. In this study, we aimed to enhance the bioavailability of gemfibrozil as well as making it more potent and less toxic by applying piperine as a bio-enhancer. Thus, piperine was co-administered to rats with gemfibrozil and the antihyperlipidemic activity was tested when fed on a high fat diet. The results showed that co-administration of gemfibrozil with piperine decreased the elevated triglyceride and cholesterol levels to normal, and they performed significantly better than the individual drugs. Weight gain was controlled effectively by drug administration together with piperine compared with other groups. Hepatic function analyses demonstrated that the potentiation of gemfibrozil did not alter the hepatic function but instead it improved significantly by normalizing the elevated serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and alkaline phosphatase levels. The plasma drug concentration of gemfibrozil was studied over time, where the enhanced activity of the drug reached its C(max) within 1 ​h of administration and the activated drug level was observed in the blood for 4 ​h.