TO STUDY THE PHARMACOKINETIC HERB-DRUG INTERACTION OF MOMORDICA CHARANTIA FRUIT EXTRACT AND PURE CHARANTIN WITH NATEGLINIDE IN RATS
Keywords:Momordica charantia extract, Charantin, NAT, Pharmacokinetic herb-drug Interaction
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.
Phillips LS, Dunning BE. Nateglinide (Starlix): update on a new antidiabetic agent. Int J Clin Pract 2003;57:535-41.
Jain R, Jain P, Jain P. A review on treatment and prevention of diabetes mellitus. Int J Curr Pharm Res 2016;8:16-8.
Tentolouris N, Voulgari C, Katsilambros N. A review of nateglinide in the management of patients with type 2 diabetes. Vasc Health Risk Manag 2007;3:797–807.
Mahmoud MF, Ashry FE, Maraghy NN, Fahmy A. Studies on the antidiabetic activities of Momordica charantia fruit juice in streptozotocin-induced diabetic rats. Pharm Biol 2017;55:758-65.
Saifi AK, Chauhan NR, Dwivedi J. Evaluation of pharmacognostical, phytochemical and antidiabetic activity fruits of momordica charantia linn. Asian J Pharm Clin Res 2014;7:152-6.
Grover JK, Yadav SP. Pharmacological actions and potential uses of Momordica charantia: a review. J Ethnopharmacol 2004;93:123–32.
Virdi J, Sivakami S, Shahani S, Suthar A, Banavalikar M, Biyani M. Antihyperglycemic effects of three extracts from Momordica charantia. J Ethnopharmacol 2003;88:107–11.
Desai S, Tatke P. Charantin: an important lead compound from Momordica charantia for the treatment of diabetes. J Pharmacogn Phytochem 2015;3:163-6.
Zhou S. Interactions of herbs with cytochrome P450. Drug Metab Rev 2003;35:35-98.
Tripathi P, Gupta PP, Lal VK. Interaction of Momordica Charantia with metformin in diabetic rats. Am J Pharmacol Toxicol 2013;8:102-6.
Pramesthi A. Drug-herb interaction between metformin and Momordica Charantia in diabetic mice. Diabetes Obes Int J 2019;4:000203.
Gupta RC, Chang D, Nammi S, Bensoussan A, Bilinski A, Roufogalis BD. Interactions between antidiabetic drugs and herbs: an overview of mechanisms of action and clinical implications. Diabetol Metab Syndr 2017;9:59.
Abdel Rahman RF, Soliman GA, Saeedan AS, Ogaly HA, Abd Elsalam RM, Alqasaumi SI, et al. Molecular and biochemical monitoring of the possible herb-drug interaction between Momordica charantia extract and glibenclamide in diabetic rats. Saudi Pharm J 2019;27:803–16.
Masafumi T, Sachiko S, Naomi K, Yoichi K. Pharmacokinetics of nateglinide enantiomers and their metabolites in goto-kakizaki rats, a model for type 2 diabetes mellitus. Chirality 2010;22:92–8.
Pani NR, Nath L, Singh AK, Mahapatra SK. Development and validation of an analytical method for the estimation of nateglinide in rabbit plasma. J Pharm Anal 2012;2:492–8.
Bauer S, Stormer K, Kirchheiner J, Michael C, Brockmller J, Roots I. Rapid and simple method for the analysis of nateglinide in human plasma using HPLC analysis with UV detection. J Pharm Biomed Anal 2003;3:551-5.
Inoue T, Shibahara N, Miyagawa K. Pharmacokinetics of nateglinide and its metabolites in subjects with type 2 diabetes mellitus and renal failure. Clin Nephrol 2003;60:90-5.
Ismail K, Rao AL. Validation of a developed analytical method for determination of nateglinide and metformin hcl in pure and pharmaceutical dosage form by reversed-phase high-performance liquid chromatography and its degradation studies. Asian J Pharm Clin Res 2021;14:196-202.
Guidance for industry, bioanalytical method validation, U. S. Department of health and human services, food and drug administration center for drug evaluation and research; 2018.
Shaikh SD, Patel A, Patel MA, Ali SA. Pharmacokinetic drug-food interaction study of nateglinide and pomegranate fruit juice. Iranian J Diabetes Obesity 2020;12:203-9.
Kanthikiran VV, Veerraghavan S, Satheeshmanikandan TRS, Shraddha R, Potharaju S, Mallick P, et al. Effect of cilostazol on pharmacokinetics of nateglinide in wistar rats. Pharma Professionals 2011;2:27-34.
Scheen AJ. Drug-drug and food-drug pharmacokinetic interactions with new insulinotropic agents repaglinide and nateglinide. Clin Pharmacokinet 2007;46:93-108.
Cheng Y, Wang G, Zhang W, Fan L, Chen Y, Zhou H. Effect of CYP2C9 and SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of nateglinide in healthy Chinese male volunteers. Eur J Clin Pharmacol 2013;69:407-13.
Derungs A, Donzelli M, Berger B, Noppen C, Krahenbuhl S, Haschke M. Effects of cytochrome P450 inhibition and induction on the phenotyping metrics of the basel cocktail: a randomized crossover study. Clin Pharmacokinet 2016;55:79–91.
How to Cite
Copyright (c) 2021 AISHWARYA R. BALAP
This work is licensed under a Creative Commons Attribution 4.0 International License.