Effect on the Gastrointestinal Absorption of Drugs from Different Classes in the Biopharmaceutics Classification System, When Treating with Liraglutide

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• 作者：Monika Malm-Erjef盲lt ; Marianne Ekblom ; Jan Vouis ; Milan Zdravkovic ; Hans Lennern盲s
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：November 2, 2015
• 年：2015
• 卷：12
• 期：11
• 页码：4166-4173
• 全文大小：454K
• ISSN：1543-8392

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 t_max (by 鈮? h) and did not meet the criterion for bioequivalence for C_max (reduced C_max by 27鈥?8%); griseofulvin had similar t_max and 37% increased C_max. 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.