文摘
Like other GLP-1 receptor agonists used for treatment of type 2 diabetes, liraglutide delays gastric emptying. In this clinical absorption study, the primary objective was to investigate the effect of liraglutide (at steady state) on the rate and/or extent of gastrointestinal (GI) absorption of concomitantly orally taken drugs from three classes of the Biopharmaceutics Classification System (BCS). To provide a general prediction on liraglutide drug鈥揹rug absorption interaction, single-dose pharmacokinetics of drugs representing BCS classes II (low solubility鈥揾igh permeability; atorvastatin 40 mg and griseofulvin 500 mg), III (high solubility鈥搇ow permeability; lisinopril 20 mg), and IV (low solubility鈥搇ow permeability; digoxin 1 mg) were studied in healthy subjects at steady state of liraglutide 1.8 mg, or placebo, in a two-period crossover design. With liraglutide, the oral drugs atorvastatin, lisinopril, and digoxin showed delayed tmax (by 鈮? h) and did not meet the criterion for bioequivalence for Cmax (reduced Cmax by 27鈥?8%); griseofulvin had similar tmax and 37% increased Cmax. Although the prespecified bioequivalence criterion was not met by all drugs, the overall plasma exposure (AUC) of griseofulvin, atorvastatin, lisinopril, and digoxin only exhibited minor changes and was not considered to be of clinical relevance.