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

• Published in: Molecular pharmaceutics Vol. 12; no. 11; pp. 4166 - 4173
• Main Authors: Malm-Erjefält, Monika, Ekblom, Marianne, Vouis, Jan, Zdravkovic, Milan, Lennernäs, Hans
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 02.11.2015
• Subjects: Administration, Oral; Adolescent; Adult; Antifungal Agents - administration & dosage; Antifungal Agents - pharmacokinetics; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - pharmacokinetics; Atorvastatin Calcium - administration & dosage; Atorvastatin Calcium - pharmacokinetics; biopharmaceutical classification systems; Biopharmaceutics - classification; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - pharmacokinetics; Computer Simulation; Cross-Over Studies; Digoxin - administration & dosage; Digoxin - pharmacokinetics; Double-Blind Method; drug interaction; Drug Interactions; Female; Gastric Emptying; Gastrointestinal Absorption; GLP-1 receptor agonist; Griseofulvin - administration & dosage; Griseofulvin - pharmacokinetics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics; Hypoglycemic Agents - pharmacology; liraglutide; Liraglutide - pharmacology; Lisinopril - administration & dosage; Lisinopril - pharmacokinetics; Male; Middle Aged; Therapeutic Equivalency; Tissue Distribution; Young Adult; liraglutide; gastrointestinal absorption; GLP-1 receptor agonist; drug interaction; biopharmaceutical classification system
• ISSN: 1543-8384; 1543-8392; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.5b00278

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–drug absorption interaction, single-dose pharmacokinetics of drugs representing BCS classes II (low solubility–high permeability; atorvastatin 40 mg and griseofulvin 500 mg), III (high solubility–low permeability; lisinopril 20 mg), and IV (low solubility–low 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 ≤2 h) and did not meet the criterion for bioequivalence for C max (reduced C max by 27–38%); 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.