title: 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.
authors.affiliation: F. Hoffmann-La Roche Ltd., Clinical Pharmacology, Basel, Switzerland. beate.bittner@actelion.com
authors.forename: Beate
authors.initials: B
authors.lastname: Bittner
authors.forename: Christine
authors.initials: C
authors.lastname: McIntyre
authors.forename: Paul
authors.initials: P
authors.lastname: Jordan
authors.forename: Johannes
authors.initials: J
authors.lastname: Schmidt
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004164:Diphosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077557:Ibandronic Acid; D008297:Male; D008687:Metformin / Q000493:pharmacokinetics / Q000494:pharmacology*; D008875:Middle Aged; D055815:Young Adult
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007004:Hypoglycemic Agents; D008687:Metformin; D000077557:Ibandronic Acid