Pharmacokinetics parameters, bioanalytical method underlying the manuscript: 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

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 two periods with a washout period of 7 days. Pharmacokinetics parameters (t_max (h), C_max (ng/ml), AUC _0-t (ng.h/ml)) as primary endpoints, and (AUC _{0 to ∞}(ng.h/ml)) as secondary endpoint 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: T_max increased by (35%) in the evening phase compared to the morning phase, while C_max decreased by (-6.5%)in the evening dose compared to the morning dose. Besides, AUC_{0 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 there was a significant difference between morning and evening doses, it didn't reach the significant level, thus, it can be concluded that there is no difference between the morning and evening doses.