Demographic data, reporting guidelines underlying the manuscript: The effect of morning versus evening administration of Empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two way cross over, non-randomized 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 (Tmax (h),
Cmax (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: 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. Besides, 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, AUC0-∞, 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.