ABSTRACT

Background: Dietary alkaloids such as piperine can cause significant pharmacodynamic and pharmacokinetic food-drug interactions which can affect drug metabolism and elimination. Piperine's impact on the pharmacodynamics and pharmacokinetics of repaglinide is investigated in this study. Method: The study was conducted in normal and diabetic rabbits to estimate the single and multi-dose interactions. In normal and diabetic rabbits, repaglinide alone and in combination with piperine were administered. Rabbits were treated for 21 days and blood samples were collected on day 1, 3, 7, 14 & day 21. For investigating the pharmacodynamic-interactions, blood glucose levels were estimated while pharmacokinetic parameters were determined to investigate the pharmacokinetic interactions. Results: The study results found that combination of piperine with repaglinide significantly decreased blood glucose levels. Additionally, the combination elicited more percent blood glucose reduction than repaglinide alone treatment in normal as well as diabetic rabbits. In pharmacokinetic studies, repaglinide with piperine significantly increased the T1/2, AUC0-t, AUC0-?, AUMC0-t, AUMC0-?, MRT0-t & MRT0-? and decreased the CL & Ke of repaglinide as compared with alone repaglinide in normal and diabetic rabbits on day 1 and day 21. The study results suggested that combination of piperine with repaglinide showed the synergistic effect on blood glucose levels and piperine substantially improved the bioavailability of repaglinide in both normal and diabetic rabbits. Conclusion: On the basis of findings obtained from pharmacodynamic and pharmacokinetic studies, it may be concluded that piperine shows significant pharmacodynamic and pharmacokinetic interactions with repaglinide thereby altering its pharmacodynamic and pharmacokinetic parameters. Thus it is recommended that diabetic individuals should be monitored on a regular basis to prevent hypoglycemic effects when repaglinide and piperine are taken together. Keywords: Piperine, repaglinide, pharmacokinetics drug interaction, diabetes, rabbits
Publication date: 01/09/2022

https://ijbpas.com/pdf/2022/September/MS_IJBPAS_2022_6408.pdf

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https://doi.org/10.31032/IJBPAS/2022/11.9.6408