title: Effect on the Gastrointestinal Absorption of Drugs from Different Classes in the Biopharmaceutics Classification System, When Treating with Liraglutide.
abstract: 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 tmax (by ≤2 h) and did not meet the criterion for bioequivalence for Cmax (reduced Cmax by 27-38%); 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.
authors.affiliation: Novo Nordisk A/S , 2860 Søborg, Denmark.
authors.forename: Monika
authors.initials: M
authors.lastname: Malm-Erjefält
authors.affiliation: Novo Nordisk A/S , 2860 Søborg, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Ekblom
authors.affiliation: Phase I Services, Quintiles AB , SE-753 23 Uppsala, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Vouis
authors.affiliation: Novo Nordisk A/S , 2860 Søborg, Denmark.
authors.forename: Milan
authors.initials: M
authors.lastname: Zdravkovic
authors.affiliation: Biopharmaceutics, Department of Pharmacy, Uppsala University , SE-751 23 Uppsala, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Lennernäs
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000069059:Atorvastatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D001702:Biopharmaceutics / Q000145:classification*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D003198:Computer Simulation; D018592:Cross-Over Studies; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005746:Gastric Emptying; D065569:Gastrointestinal Absorption; D006118:Griseofulvin / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000069450:Liraglutide / Q000494:pharmacology*; D017706:Lisinopril / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D006118:Griseofulvin; D004077:Digoxin; D000069450:Liraglutide; D000069059:Atorvastatin; D017706:Lisinopril
keywords: GLP-1 receptor agonist; biopharmaceutical classification system; drug interaction; gastrointestinal absorption; liraglutide