Dataset Information

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.

ABSTRACT: 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: t _max (h), C _max (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: 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. Additionally, 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 the difference in pharmacokinetics parameters between evening and morning doses, C _max, AUC _0-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 29 ^th March 2019).

SUBMITTER: ElDash RM

PROVIDER: S-EPMC8167502 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Torasemide is a loop diuretic licensed in dogs for cardiogenic pulmonary oedema. The aim of this pharmacokinetic-pharmacodynamic (PK/PD) study was to define an optimally effective dosage regimen based on preclinical data. In a first study, 5 dogs received once-daily oral torasemide (0, 0.1, 0.2, 0.4, 0.8 mg/kg/day) for 14 days. A second study compared once-daily oral torasemide (0, 0.1, 0.2, 0.3, 0.4 mg/kg/day) to twice-daily furosemide (1, 2, 4, 8 mg/kg/day). For all doses of the second study, 11 dogs received a first day of treatment, followed by a 3 day washout and resumed daily treatment for 10 days (until Day 14). Blood and urine were collected to measure urinary torasemide excretion and plasma torasemide concentrations and daily diuresis and natriuresis. Torasemide PK was linear. After rapid absorption (Tmax 0.5-1 h), 61% of the bioavailable torasemide was eliminated unchanged in urine. Diuresis and natriuresis observed with torasemide were similar to the ones obtained after furosemide (daily dose-ratios: 1/20 to 1/10). The average diuresis increased from baseline (220 ± 53 mL/day for 10 kg dogs) to 730 ±120 mL after the first torasemide administration and up to 1150 ± 252 mL after 10 administrations at the highest dose. At higher doses (≥0.3 mg/kg/day), daily diureses after 10 diuretic treatment-days were higher than Day 1 and variable between dogs; in contrast, diureses remained constant over time and less variable for doses up to 0.2 mg/kg/day. Natriuresis peaked after the first day and decreased dramatically after the 2nd treatment-day then stabilized to a value close to baseline, except for 0.4 mg/kg/day. Urinary torasemide excretion predicted pharmacodynamics better than plasma concentrations. The decrease in natriuresis observed was successfully modeled using a resistance mechanism; this is likely due to a reabsorption of sodium which did not seem however to affect the volume of urine excreted. For a daily target diuresis of 460 mL/dog/day in severe pulmonary oedema (net fluid loss 240 mL/dog/day), a computed dose of 0.26 mg/kg/day (3.5 mg/kg/day furosemide-equivalent) was selected for clinical studies. Due to high inter-individual variability in diureses at doses ≥0.3 mg/kg, higher doses should be limited to 3-5 days to avoid supra-clinical effects in high responders.

Project description:Post-exercise hypotension (PEH), calculated by the difference between post and pre-exercise values, it is greater after exercise performed in the evening than the morning. However, the hypotensive effect of morning exercise may be masked by the morning circadian increase in blood pressure. This study investigated PEH and its hemodynamic and autonomic mechanisms after sessions of aerobic exercise performed in the morning and evening, controlling for responses observed after control sessions performed at the same times of day. Sixteen pre-hypertensive men underwent four sessions (random order): two conducted in the morning (7:30 am) and two in the evening (5 pm). At each time of day, subjects underwent an exercise (cycling, 45 min, 50%VO2peak) and a control (sitting rest) session. Measurements were taken pre- and post-interventions in all the sessions. The net effects of exercise were calculated for each time of day by [(post-pre exercise)-(post-pre control)] and were compared by paired t-test (P<0.05). Exercise hypotensive net effects (e.g., decreasing systolic, diastolic and mean blood pressure) occurred at both times of day, but systolic blood pressure reductions were greater after morning exercise (-7±3 vs. -3±4 mmHg, P<0.05). Exercise decreased cardiac output only in the morning (-460±771 ml/min, P<0.05), while it decreased stroke volume similarly at both times of day and increased heart rate less in the morning than in the evening (+7±5 vs. +10±5 bpm, P<0.05). Only evening exercise increased sympathovagal balance (+1.5±1.6, P<0.05) and calf blood flow responses to reactive hyperemia (+120±179 vs. -70±188 U, P<0.05). In conclusion, PEH occurs after exercise conducted at both times of day, but the systolic hypotensive effect is greater after morning exercise when circadian variations are considered. This greater effect is accompanied by a reduction of cardiac output due to a smaller increase in heart rate and cardiac sympathovagal balance.

Dataset Information

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets