The effect of morning versus evening administration of empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two-way crossover, non-randomised trial [version 1; peer review: 2 approved, 1 approved with reservations]

Background: Empagliflozin is an SGLT2 inhibitor approved for use in patients with diabetes mellitus type 2 (DMT2) with or without other cardiovascular disease. Empagliflozin is taken once daily without rationale on the optimal timing for administration. This study aimed to determine the chronopharma...

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Main Authors: Rana M. ElDash, Mohamed A. Raslan, Sara M. Shaheen, Nagwa Ali Sabri
Format: Article
Language:English
Published: F1000 Research Ltd 2021-04-01
Series:F1000Research
Online Access:https://f1000research.com/articles/10-321/v1
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spelling doaj-3d3d1e0e704f4f898ace4a52979039442021-06-02T10:58:47ZengF1000 Research LtdF1000Research2046-14022021-04-011010.12688/f1000research.51114.154231The effect of morning versus evening administration of empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two-way crossover, non-randomised trial [version 1; peer review: 2 approved, 1 approved with reservations]Rana M. ElDash0Mohamed A. Raslan1Sara M. Shaheen2Nagwa Ali Sabri3Pharmacy Practice Department, Faculty of Pharmacy, Heliopolis University, Cairo, 11785, EgyptQuality Control, Drug Research Center, Cairo, EgyptClinical Pharmacy Department, Faculty of Pharmacy, AinShms University, Cairo, 11566, EgyptClinical Pharmacy Department, Faculty of Pharmacy, AinShms University, Cairo, 11566, EgyptBackground: Empagliflozin is an SGLT2 inhibitor approved for use in patients with diabetes mellitus type 2 (DMT2) with or without other cardiovascular disease. Empagliflozin is taken once daily without rationale on the optimal timing for administration. This study aimed to determine the chronopharmacological effects of morning vs evening administration of empagliflozin (10 mg) in healthy Egyptian adults, by investigating the pharmacokinetics and pharmacodynamics parameters of empagliflozin depending on the intake time. Methods: An open label, sequential, two‐way crossover trial comprised of two periods with a washout period of 7 days. All participants received a single oral dose of empagliflozin (JARDIANCE ®; 10 mg film coated tablet) in the evening, and after a seven-day washout period, the morning. Pharmacokinetics parameters (primary endpoints: tmax (h), Cmax (ng/ml), AUC 0-t (ng.h/ml); secondary endpoints: AUC 0 to ∞(ng.h/ml)) were assessed. Method validation was done prior to injection in LC/MS/MS and samples were processed by Liquid-Liquid extraction. The pharmacodynamic profile (UGE 0-24) was determined after method validation (glucose hexokinase method). Results: Tmax increased by 35% in the evening phase compared to the morning phase, while Cmax decreased by -6.5% in the evening dose compared to the morning dose. Additionally, AUC0 to ∞ increased in the evening phase by 8.25% compared to the morning phase. The mean cumulative amount of glucose excreted (UGE (0-24)) increased by 43% in the evening dose compared to the morning dose Conclusion: Despite the difference in pharmacokinetics parameters between evening and morning doses, Cmax, AUC0-t, AUC 0-∞, didn’t differ on the bioequivalence level. In addition, as UGE (0-24) didn’t statistically differ, thus, we can conclude that there is no statistical significance between the morning and evening doses. Trial registration: Clinal Trials.gov, ID: NCT03895229 (registered on 29th March 2019).https://f1000research.com/articles/10-321/v1
collection DOAJ
language English
format Article
sources DOAJ
author Rana M. ElDash
Mohamed A. Raslan
Sara M. Shaheen
Nagwa Ali Sabri
spellingShingle Rana M. ElDash
Mohamed A. Raslan
Sara M. Shaheen
Nagwa Ali Sabri
The effect of morning versus evening administration of empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two-way crossover, non-randomised trial [version 1; peer review: 2 approved, 1 approved with reservations]
F1000Research
author_facet Rana M. ElDash
Mohamed A. Raslan
Sara M. Shaheen
Nagwa Ali Sabri
author_sort Rana M. ElDash
title The effect of morning versus evening administration of empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two-way crossover, non-randomised trial [version 1; peer review: 2 approved, 1 approved with reservations]
title_short The effect of morning versus evening administration of empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two-way crossover, non-randomised trial [version 1; peer review: 2 approved, 1 approved with reservations]
title_full The effect of morning versus evening administration of empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two-way crossover, non-randomised trial [version 1; peer review: 2 approved, 1 approved with reservations]
title_fullStr The effect of morning versus evening administration of empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two-way crossover, non-randomised trial [version 1; peer review: 2 approved, 1 approved with reservations]
title_full_unstemmed The effect of morning versus evening administration of empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two-way crossover, non-randomised trial [version 1; peer review: 2 approved, 1 approved with reservations]
title_sort effect of morning versus evening administration of empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two-way crossover, non-randomised trial [version 1; peer review: 2 approved, 1 approved with reservations]
publisher F1000 Research Ltd
series F1000Research
issn 2046-1402
publishDate 2021-04-01
description Background: Empagliflozin is an SGLT2 inhibitor approved for use in patients with diabetes mellitus type 2 (DMT2) with or without other cardiovascular disease. Empagliflozin is taken once daily without rationale on the optimal timing for administration. This study aimed to determine the chronopharmacological effects of morning vs evening administration of empagliflozin (10 mg) in healthy Egyptian adults, by investigating the pharmacokinetics and pharmacodynamics parameters of empagliflozin depending on the intake time. Methods: An open label, sequential, two‐way crossover trial comprised of two periods with a washout period of 7 days. All participants received a single oral dose of empagliflozin (JARDIANCE ®; 10 mg film coated tablet) in the evening, and after a seven-day washout period, the morning. Pharmacokinetics parameters (primary endpoints: tmax (h), Cmax (ng/ml), AUC 0-t (ng.h/ml); secondary endpoints: AUC 0 to ∞(ng.h/ml)) were assessed. Method validation was done prior to injection in LC/MS/MS and samples were processed by Liquid-Liquid extraction. The pharmacodynamic profile (UGE 0-24) was determined after method validation (glucose hexokinase method). Results: Tmax increased by 35% in the evening phase compared to the morning phase, while Cmax decreased by -6.5% in the evening dose compared to the morning dose. Additionally, AUC0 to ∞ increased in the evening phase by 8.25% compared to the morning phase. The mean cumulative amount of glucose excreted (UGE (0-24)) increased by 43% in the evening dose compared to the morning dose Conclusion: Despite the difference in pharmacokinetics parameters between evening and morning doses, Cmax, AUC0-t, AUC 0-∞, didn’t differ on the bioequivalence level. In addition, as UGE (0-24) didn’t statistically differ, thus, we can conclude that there is no statistical significance between the morning and evening doses. Trial registration: Clinal Trials.gov, ID: NCT03895229 (registered on 29th March 2019).
url https://f1000research.com/articles/10-321/v1
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