TO STUDY THE PHARMACOKINETIC HERB-DRUG INTERACTION OF MOMORDICA CHARANTIA FRUIT EXTRACT AND PURE CHARANTIN WITH NATEGLINIDE IN RATS

Aishwarya R Balap

doi:10.22159/ijpps.2021v13i9.40967

Abstract

Objective: Momordica charantia fruit extract and antidiabetic drug Nateglinide might be used simultaneously in the treatment of diabetes, so the objective of this study was to investigate pharmacokinetic herb-drug interactions of Momordica charantia fruit extract and pure charantin with nateglinide in rats. Methods: After oral co-administration of Momordica charantia fruit extract (250 mg/kg) and Charantin (10 mg/kg) with nateglinide in rats, drug concentration parameters peak plasma concentration (Cmax), time to reach peak plasma concentration (tmax), elimination half-life (t1/2), apparent volume of distribution (Vd), plasma clearance (Cl), and area under the curve (AUC) were calculated by using the non-compartment model. Results: NAT was absorbed into the circulatory system and reached its peak concentration approximately 2 h after being administered individually. tmax of groups co-administered NAT+MCE has been changed to 4h. A significant decrease in Cmax of NAT from 16.28 µg/ml to 11.37 µg/ml and 10.37 µg/ml with NAT with charantin and NAT with MCE groups, respectively. AUC of NAT decreased from 84.53 h/µg/ml to 53.63 h/µg/ml and 47.17 h/µg/ml by co-administration with Charantin and MCE respectively. Co-administration of nateglinide with Charantin and Momordica charantia fruit extract decreased systemic exposure level of nateglinide in vivo with decreasing Cmax and AUC and an increase in t1/2, Cl and Vd. Conclusion: From this study, it can be concluded that nateglinide, Momordica charantia fruit extract, and pure Charantin existed pharmacokinetic herb-drug interactions in the rat which has to be correlated with the anti-diabetic study. Further studies should be done to understand the effect of other herbal ingredients of Momordica charantia fruit extract on nateglinide as well as to predict the herb-drug interaction in humans.

Highlights

Nateglinide ((2R)-3-phenyl-2-[(4-propan-2-ylcyclohexanecarbonyl) amino]propanoic acid.) (NAT fig. 1) belongs to class of meglitinide used in the treatment of diabetes [1,2,3]
NAT absorbed into the circulatory system and reached its peak concentration approximately 2 h after administered individually. tmax of groups co-administered NAT+Charantin was the same, but tmax of group co-administered NAT+Momordica charantia extract (MCE) has been changed to 4h, respectively
Coadministration of NAT with MCE significantly (P 0.05) decreased the Cmax, area under the curve (AUC), Ke and increased the tmax, t1/2, Cl, and volume of distribution (Vd) of NAT when compared to NAT alone group

Summary

Introduction

Nateglinide ((2R)-3-phenyl-2-[(4-propan-2-ylcyclohexanecarbonyl) amino]propanoic acid.) (NAT fig. 1) belongs to class of meglitinide used in the treatment of diabetes [1,2,3]. Momordica charantia (MC) is a part of the cucurbitaceae family. It grows in tropical areas of India, Amazon, East Africa, Asia, and South America. Fruits are used as a traditional medication for the treatment of diseases like illness of the liver, worms, colic spleen, rheumatism, gout, and useful in the treatment of diabetes and cancer. It is a potent hypoglycemic agent due to the presence of insulin and alkaloids like a mixture of steroidal sapogenins and peptides known as charantin. Charantin (fig. 1), an active constituent in the fruits of this medicinal plant, has been reported to have potential hypoglycemic activity [8]

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Discussion

Conclusion