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A randomized, open-label, crossover study evaluating the effect of food on the relative bioavailability of linagliptin in healthy subjects.
Clin Ther. 2011 Aug; 33(8):1096-103.CT

Abstract

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.

Authors+Show Affiliations

Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany. Ulrike.Graefe-Mody@boehringer-ingelheim.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21803422

Citation

Graefe-Mody, Ulrike, et al. "A Randomized, Open-label, Crossover Study Evaluating the Effect of Food On the Relative Bioavailability of Linagliptin in Healthy Subjects." Clinical Therapeutics, vol. 33, no. 8, 2011, pp. 1096-103.
Graefe-Mody U, Giessmann T, Ring A, et al. A randomized, open-label, crossover study evaluating the effect of food on the relative bioavailability of linagliptin in healthy subjects. Clin Ther. 2011;33(8):1096-103.
Graefe-Mody, U., Giessmann, T., Ring, A., Iovino, M., & Woerle, H. J. (2011). A randomized, open-label, crossover study evaluating the effect of food on the relative bioavailability of linagliptin in healthy subjects. Clinical Therapeutics, 33(8), 1096-103. https://doi.org/10.1016/j.clinthera.2011.07.005
Graefe-Mody U, et al. A Randomized, Open-label, Crossover Study Evaluating the Effect of Food On the Relative Bioavailability of Linagliptin in Healthy Subjects. Clin Ther. 2011;33(8):1096-103. PubMed PMID: 21803422.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A randomized, open-label, crossover study evaluating the effect of food on the relative bioavailability of linagliptin in healthy subjects. AU - Graefe-Mody,Ulrike, AU - Giessmann,Thomas, AU - Ring,Arne, AU - Iovino,Mario, AU - Woerle,Hans-Juergen, Y1 - 2011/07/30/ PY - 2011/07/07/accepted PY - 2011/8/2/entrez PY - 2011/8/2/pubmed PY - 2011/12/14/medline SP - 1096 EP - 103 JF - Clinical therapeutics JO - Clin Ther VL - 33 IS - 8 N2 - 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. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/21803422/A_randomized_open_label_crossover_study_evaluating_the_effect_of_food_on_the_relative_bioavailability_of_linagliptin_in_healthy_subjects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(11)00490-5 DB - PRIME DP - Unbound Medicine ER -