Pharmacokinetic Interaction of Tinospora cordifolia with Co administered Antidiabetic drugs

Abstract

newline Diabetes, one of the lifestyle disorders; has a pandemic existence in today s world. newlineAbout three fourth of the total population suffering from diabetes use complementary and newlinealternative medicines (CAM) along with modern medicine [Egede et al., 2002]. Herbal newlinedrugs are generally considered to be safe and preferred as CAM due to their holistic effects. newlineConsidering the multi-component profiles of herbal drugs, their pharmacokinetic and newlinePharmacodynamic interaction with co-administered drugs can be expected. Thus, scientific newlinevalidation of their interaction with co-administered drugs should get priority before their newlineuse as CAM. newlineTinospora cordifolia (TC) from family Menispermaceae is a key herb in Ayurvedic newlineliterature as a tonic, vitalizer and as a remedy for diabetes and other metabolic disorders. newlineBased on its ethnopharmacology, supported by wide investigations [Ahmed, Siddaraju and newlineUrooj, 2011; Grover, Rathi and Vats, 2002)], TC is the preferred herbal drug to reduce newlineblood glucose levels. Accordingly, it is the major herbal drug used as CAM in diabetes. newlineMetformin (MET) and Glibenclamide (GLI) are the drugs of choice in type 2 diabetes. newlineAlthough, the pharmacodynamic/pharmacokinetic interaction of TC with these drugs is not newlineknown; in many instances, TC is used along with these drugs. Thus, it is of prime interest newlineto understand the interaction of TC with MET and GLI. newlineIn the current study, an effort has been made to study the pharmacokinetic newlineinteractions of authentic TC extract (TCE) with two of commonly used antidiabetic drug newlineMET and GLI in normal rats. In the first part, TCE was co-administered in two different newlinegroups (10 and 100 mg/kg) with MET at 30 mg/kg dose to observe the alteration in newlinepharmacokinetic parameters of MET in two independent pharmacokinetic studies. In the newlinefirst pharmacokinetic study, rats were co-administered with a singledose of MET and two newlinedifferent doses of TCE (10 and 100 mg/kg). In the second pharmacokinetic study, the rats newlinewere pretreated with 10 and 100 mg/kg dose of TCE b.i.d for 14 days along with a vehicletreated newlinegroup. On the 14th day, all three groups were dosed with 30 mg/kg MET. Plasma newlineconcentration of MET from both the studies was analyzed by newly developed LC-MS newlinemethods using acyclovir as an internal standard. Pharmacokinetic study parameters viz. newlinepeak plasma concentration (Cmax), time needed to reach the peak plasma concentration newlineix newline(Tmax), area under the plasma concentration time curve (AUC0-inf), the clearance (Cl) and newlinehalf-life (t1/2) was calculated using Phoenix® WinNonlin® software. newlineAs GLI is known to be metabolized by CYP enzymes [Fda.gov, 2009], CYP newlineinhibition studies and metabolism studies were done to provide supportive evidence for