Translational evaluation of Metformin in combination with Rutin and L-theanine: Integrative pharmacokinetic and pharmacodynamic perspectives in an animal model of type 2 diabetes
Abstract
ABSTRACT Background Rutin (芦丁) and L-theanine(茶氨酸) are notable bioactive compounds employed in traditional Chinese medicine (TCM) for their diverse therapeutic effects. With the increasing global burden of Diabetes mellitus, the concurrent use of herbal supplements along with conventional therapy has become a routine practice. The present study evaluated the pharmacokinetic–pharmacodynamic interactions of Rutin and L-theanine with Metformin in preclinical models to provide preliminary translational insights into herb–drug interactions in diabetes management. Methods Male wistar rats weighing about 160-230 g were included in the study. Intraperitoneal administration of a single dose of Nicotinamide (100 mg/kg) and Streptozotocin (50 mg/kg) induced Type 2 diabetes. The normal and diabetic rats were treated with 100 mg/kg dose of Metformin alone and in combination with 20 mg/kg dose of Rutin or 50 mg/kg dose of L-theanine for an experimental period of 21 days. Results Diabetes impeded Metformin absorption, while the simultaneous administration of a single dose of Rutin or L-theanine partially altered its pharmacokinetic profile in diabetic rats. Rutin diminished systemic exposure despite improved absorption kinetics, whereas L-theanine augmented the absorption rate without influencing systemic exposure in diabetic rats. The repeated co-administration of Rutin or L-theanine did not result in significant pharmacokinetic alterations in normal rats; however, in diabetic rats,…
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