An in-vivo herb-drug interaction study of Tinospora cordifolia extract on the pharmacokinetics of gliclazide in normal Wistar rats

Abstract

Background and Aims: Tinospora cordifolia (Willd.) Miers (TC), from the Menispermaceae family, is a well-known traditional herb used to treat diabetes mellitus and a variety of other ailments, according to traditional Indian literature. Herbal treatments are commonly used as alternatives to medicines. Anti-diabetic herbal medicines containing TC are available in the market. TC has been identified as a powerful CYP2C9 inhibitor, boosting the risk of herb-drug interactions (HDI) when used with medications metabolized via the CYP pathway. The present study evaluated the pharmacokinetic HDI of TC extract with Gliclazide (GL) after oral co-administration in Wistar rats using in vivo pharmacokinetic studies. Methods: A simple, sensitive & accurate RP-HPLC/PDA method was developed and validated. Chromatographic separations were performed on a C18 analytical column with a mobile phase of acetonitrile and 40 mM ammonium acetate buffer (55:45 v/v) pH 3.0 and flow rate gradient programming. The drug concentrations in plasma were measured using the RP-HPLC method after oral co-administration of TC extract (100 mg/kg) with GL (8.3 mg/kg) in Wistar rats. Results: The pharmacokinetic (PK) interaction studies showed that the bioavailability of GL had significantly increased, with a significant influence on Cmax, AUC0-48, and suppression of volume of distribution (Vd), with no change in Tmax. Conclusion: The results obtained from this in vivo study proposed that there is a potentially significant PK HDI when GL and TC extract are administered together. This knowledge of potential HDI could be beneficial to healthcare providers and diabetic patients on GL medication. Further research is needed to anticipate this pharmacokinetics HDI of GL in humans.