Document Detail

A randomized, open-label, crossover study evaluating the effect of food on the relative bioavailability of linagliptin in healthy subjects.
MedLine Citation:
PMID:  21803422     Owner:  NLM     Status:  MEDLINE    
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.
Ulrike Graefe-Mody; Thomas Giessmann; Arne Ring; Mario Iovino; Hans-Juergen Woerle
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2011-07-30
Journal Detail:
Title:  Clinical therapeutics     Volume:  33     ISSN:  1879-114X     ISO Abbreviation:  Clin Ther     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-17     Completed Date:  2011-12-12     Revised Date:  2013-05-13    
Medline Journal Info:
Nlm Unique ID:  7706726     Medline TA:  Clin Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1096-103     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.
Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
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MeSH Terms
Area Under Curve
Biological Availability
Chromatography, High Pressure Liquid
Cross-Over Studies
Dipeptidyl-Peptidase IV Inhibitors / adverse effects,  pharmacokinetics*
Food-Drug Interactions*
Middle Aged
Purines / adverse effects,  pharmacokinetics*
Quinazolines / adverse effects,  pharmacokinetics*
Tandem Mass Spectrometry
Young Adult
Reg. No./Substance:
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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