Pharmacodynamics parameters 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 (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 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.

Methods
Urine samples were collected by urine collecting tube (1liter) for determination of UGE in g (urinary glucose excretion), which is the mean amount of glucose excreted in urine over the first 24 h after oral administration. Sampling intervals were 0 to 4, 4 to 8, 8 to 12 and 12 to 24 h after the administration of empagliflozin at the morning and evening doses.

Samples were stored at -80°C before being sent to the clinical laboratory for analysis.

Analysis was done by usin: Glucose hexokinase method.

https://www.sciencedirect.com/science/article/abs/pii/S0308814615006172?via%3Dihub (link to Glucose hexokinase method)