| A randomized, open-label, crossover study evaluating the effect of food on the relative bioavailability of linagliptin in healthy subjects. | |
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MedLine Citation:
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PMID: 21803422 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The objective of this study was to determine the relative bioavailability of the dipeptidyl-peptidase-4 (DPP-4) inhibitor linagliptin when administered with and without food, in accordance with regulatory requirements to support dosing recommendations for patients. METHODS: This was a randomized, open-label, crossover study involving 32 healthy white male and female subjects. All subjects received a single dose of 5 mg linagliptin after an overnight fast of at least 10 hours, or immediately after ingestion of a high-fat, high-calorie breakfast. These treatments were separated by a period of 5 weeks. Plasma samples for pharmacokinetic analysis were collected before dosing and at prespecified time points after dosing. The concentration of linagliptin in these samples was analyzed by high-performance liquid chromatography coupled to tandem mass spectrometry. Relative bioavailability was assessed by the total area under the curve between 0 and 72 hours (AUC(0-72)) and maximum measured plasma concentration (C(max)) of linagliptin. Tolerability was also assessed. RESULTS: In 32 subjects (mean age, 34.8 years; weight, 74.3 kg; male, 53%; white race, 100%), intake of a high-fat meal resulted in comparable bioavailability with regard to AUC(0-72) (geometric mean ratio [GMR] between the fed and fasted group means was 103.5%; 90% CI, 98.1%-109.2%). Individuals' responses to food ranged from a maximum increase in exposure of 38% to a decrease of 32% relative to the fasted state. The concurrent intake of food increased the time to reach maximum plasma concentration (T(max)) by approximately 2 hours and reduced C(max) by about 15% (GMR 84.7%; 90% CI, 75.9%-94.6%). Since adequate drug exposure for inhibition of DPP-4 was still given for the entire 24-hour dosing interval, this result was considered to be of no clinical relevance. Linagliptin was well tolerated during the study. CONCLUSIONS: Intake of a high-fat meal reduced the rate of linagliptin absorption but had no influence on the extent of absorption; this finding suggests that food has no relevant influence on the efficacy of linagliptin. |
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Authors:
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Ulrike Graefe-Mody; Thomas Giessmann; Arne Ring; Mario Iovino; Hans-Juergen Woerle |
Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2011-07-30 |
Journal Detail:
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Title: Clinical therapeutics Volume: 33 ISSN: 1879-114X ISO Abbreviation: Clin Ther Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-17 Completed Date: 2011-12-12 Revised Date: 2013-05-13 |
Medline Journal Info:
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Nlm Unique ID: 7706726 Medline TA: Clin Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1096-103 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved. |
Affiliation:
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Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany. Ulrike.Graefe-Mody@boehringer-ingelheim.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Area Under Curve Biological Availability Chromatography, High Pressure Liquid Cross-Over Studies Dipeptidyl-Peptidase IV Inhibitors / adverse effects, pharmacokinetics* Female Food-Drug Interactions* Humans Male Middle Aged Purines / adverse effects, pharmacokinetics* Quinazolines / adverse effects, pharmacokinetics* Tandem Mass Spectrometry Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Dipeptidyl-Peptidase IV Inhibitors; 0/Purines; 0/Quinazolines; 3X29ZEJ4R2/Linagliptin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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