Research J. Pharm. and Tech. 16(3): March 2023 991 ISSN 0974-3618 (Print) www.rjptonline.org 0974-360X (Online) RESEARCH ARTICLE Effect of Capsaicin on Pharmacokinetics and Pharmacodynamics of Nateglinide in normal and diabetic rats Naga Raju Kandukoori 1 , Narsimha Reddy Yellu 2 * 1 Department of Pharmaceutics, St. Pauls College of Pharmacy, Turkayamjal (V), Ranga Reddy (D), Hyderabad, Telangana, India. 2 University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana – India. *Corresponding Author E-mail: ynrku@kakatiya.ac.in ABSTRACT: The Cytochrome P-450 (CYP) enzymes present in the human body are responsible for the metabolism of most antidiabetic drugs. These CYP enzymes may metabolize the drugs either to active metabolites or to inactive metabolites. Some phytoconstituents which are present in vegetables, fruits and ayurvedic products will alter the activity of CYP enzymes. In the present research, the alterations in pharmacokinetics and pharmacodynamics of Nateglinide in the presence of a phytochemical like Capsaicin were studied. The study was conducted both in normal and diabetic rats. Rats were divided into different groups. Drug was administered as alone in one group and administered in combination with Capsaicin to other groups. After 8 days of treatment, the blood samples were collected and analysed. The Pharmacokinetic parameters like Cmax, tmax, AUC, MRT, Vd and ClT were estimated for all groups and compared. The mean blood glucose levels before and after treatments were recorded and compared among the groups. From the results, it could be concluded that the Capsaicin has inhibited the activity of CYP 2C9 and CYP 3A4 enzymes, thereby decreased the metabolism of drug which ultimately resulted in the increase of Cmax and AUC. The Capsaicin could raise the antidiabetic effect of drug. KEYWORDS: Capsaicin, Nateglinide, Pharmacokinetics, Pharmacodynamics, CYP 2C9 and CYP 3A4. INTRODUCTION: The bioavailability of administered drugs will be decided by the Cytochrome-P450 (CYP) enzymes present in human body. The chemical form of the administered drug may be changed due to metabolism by CYP enzymes. The converted forms may be active or inactive. Being the substrates for these CYP enzymes, most of the antidiabetic drugs are metabolized by these enzymes. The activity of CYP enzymes may be inhibited or induced by many phytoconstituents. These phytoconstituents affect the extent of metabolism of antidiabetic drugs which are metabolized by CYP enzymes. As a result, the pharmacokinetics of antidiabetic drugs will be affected 1 . The major sources of these phytochemicals are dietary fruits, vegetables, some medicinal plants and some antidiabetic ayurvedic products. These phytoconstituents also show therapeutic activities. Received on 02.09.2020 Modified on 18.12.2020 Accepted on 20.02.2021 © RJPT All right reserved Research J. Pharm. and Tech 2023; 16(3):991-996. DOI: 10.52711/0974-360X.2023.00165 If the phytoconstituents with antidiabetic activity are ingested along with synthetic antidiabetic drug, there will be synergistic effect leading to enhanced antidiabetic property (alteration of pharmacodynamics). If the phytoconstituents are ingested by a patient on antidiabetic drug therapy, there will be a chance of alteration of both pharmacokinetics and pharmacodynamics of administered drug. As a result, there will be alteration in final therapeutic efficacy of antidiabetic drug 2 . Capsaicin (trans-8-methyl-N-vanilly-6-nonenamide) is the active phytoconstituents present in the fruits of Capsicum annum (Solanaceae family). The hot pungent taste of chilli peppers is mainly caused by Capsaicin. Capsaicin constitutes as main ingredient in many spicy foods consumed throughout the world. It possesses antidiabetic activity and the activity of CYP enzymes like CYP2C9 and CYP 3A4 is inhibited by Capsaicin 3 . In the previous literature, it was reported that the bioavailability (there by pharmacokinetics and pharmacodynamics) of drugs such as simvastatin, galantamine and gliclazide was altered by Capsaicin 3-7 .