Drug-drug interaction study between a novel oral ibandronate formulation and metformin

Abstract

The novel excipient, sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC, CAS 203787-91-1) increases the oral bioavailability of co-formulated ibandronate (IBN, CAS 138926-19). The aim of this study was to investigate the effect of the IBN/SNAC formulation on the steady-state pharmacokinetics of metformin (CAS 657-24-9) and to assess safety and tolerability of IBN/SNAC when dosed in combination with metformin. Twenty-two healthy subjects received metformin on Days 1 to 6. On Day 7, subjects received metformin together with the IBN/ SNAC formulation. The safety and tolerability of IBN/SNAC co-administered with metformin was consistent with the known safety profile of the single medications. The increase in mean maximum plasma concentration (Cmax) and mean overall exposure to metformin (AUC0-tau,) was approximately 7%. The entire 90% confidence intervals for the AUC- and Cmax-ratios did fall within the acceptance region for bioequivalence (0.8-1.25). In summary, administration of the IBN/ SNAC formulation together with metformin did not lead to a significant increase in exposure to metformin. The study medication was well tolerated in healthy volunteers.