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 ...背景：恩格列净是一种钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂，已获批用于伴或不伴其他心血管疾病的2型糖尿病（Diabetes Mellitus type 2, DMT2）患者。该药每日给药一次，但目前尚无最佳给药时机的相关依据。本研究旨在通过探究不同服药时间下恩格列净的药代动力学与药效动力学参数，明确10 mg恩格列净晨间与晚间给药在健康埃及成人受试者中的时辰药理学效应。 方法：本研究为开放标签、序贯式双向交叉试验，包含两个试验阶段，阶段间洗脱期为7天。本研究评估的主要终点为药代动力学参数：达峰时间（tmax，单位：小时）、峰浓度（Cmax，单位：纳克/毫升）、0-t时间曲线下面积（AUC₀-t，单位：纳克·小时/毫升）；次要终点为0至无穷大时间曲线下面积（AUC₀→∞，单位：纳克·小时/毫升）。在采用液相色谱-串联质谱（LC/MS/MS）进行检测前，已完成方法学验证，样本处理采用液液萃取法。方法学验证完成后，测定了药效学指标（0-24小时尿糖排泄量UGE₀-24，葡萄糖……）