Ruzu herbal bitters altered the pharmacokinetic profile of metformin tablets in healthy Nigerian volunteers following concurrent administration

Background: Ruzu® Herbal bitters (RHB) is a commercial polyherbal formulation made from a blend of various parts and fruits of plant of Uvaria chamae P. Beauv., Curculigo pilosa Schumach. & Thonn and Citrullus colocynthis (L) Schrad. It is claimed to be used for the management of diabetes, cure weak erection in men, boost the immune system and effective against typhoid and malaria.

Objectives: This study was carried out to investigate the potential interactions between metformin tablets when co-administered with RHB.

Methods: A total of ten healthy volunteers were recruited and assigned into two groups. One group ingested 500 mg single dose metformin tablet orally using table water while the other group took 30 mL of the herbal formulation daily for 4 days, followed by 500 mg single oral dose of metformin tablet taken with same volume of the bitters on the fifth day. Blood samples were collected and analyzed using a validated High performance Liquid Chromatography.

Results: All the pharmacokinetic parameters evaluated were altered in the presence of RHB. The terminal half-life (t1/2, p = 0.01), apparent volume of distribution (Vd/F, p = 0.008), systemic clearance (Cl/F, p = 0.034) and mean residence time (MRT, p = 0.03) were reduced while terminal elimination rate constant (Kel, p = 0.005) was elevated with Ruzu herbal bitters. This influence is likely mediated by competitive inhibition or induction of the metformin transporters such as organic cation transporter-1(OCT-1), Plasma membrane monoamine transporter (PMAT) by the phytochemical constituents of RHB. The changes observed were statistically significant for the t1/2, Kel, Vd/F, Cl/F and MRT (p < 0.05).

Conclusion: The results obtained from the study showed that co-administration of metformin and RHB altered the pharmacokinetic parameters of Metformin.