Pharmacokinetic Evaluation of Empagliflozin in Healthy Egyptian Volunteers Using LC-MS/MS and Comparison with Other Ethnic Populations

Abstract

The present study considered the pharmacokinetic evaluation of empagliflozin after administration to Egyptian volunteers, and the results were compared with other ethnic populations. The FDA recognizes that standard methods of defining racial subgroups are necessary to compare results across pharmacokinetic studies and to assess potential subgroup differences. The design of the study was as an open labeled, randomized, one treatment, one period, single dose pharmacokinetic study. The main pharmacokinetic parameters estimated were Cmax, Tmax, t1/2, elimination rate constant, AUC0-t and AUC0-inf. The insignificant difference in pharmacokinetic parameters between Egyptians and white German subjects suggests that no dose adjustment should be considered with administration of 25 mg empagliflozin to Egyptian population. A new LC-MS/MS method was developed and validated, allowing sensitive estimation of empagliflozin (25–600 ng mL−1) in human plasma using dapagliflozin as an internal standard (IS). The method was applied successfully on the underlying pharmacokinetic study with enhanced sample preparation that involved liquid-liquid extraction. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 449.01 to 371.21 for empagliflozin and m/z 407.00 to 328.81 for dapagliflozin (IS) was employed utilizing negative mode Electro Spray Ionization (ESI). The validated LC-MS/MS method is suitable for further toxicodynamic and bioequivalence studies.

Avoiding COVID-19 Complications with Diabetic Patients Could Be Achieved by Multi-Dose Bacillus Calmette–Guérin Vaccine: A Case Study of Beta Cells Regeneration by Serendipity

“…BCG multi-dose clinical trials in Egypt may show different results than those obtained from US volunteers' multi-dose long term study that was targeting diabetes [26] due to ethnic and genetic factors [27][28][29]. Ethnic difference has been taken in consideration in recent years.…”

A UPLC/DAD method for simultaneous determination of empagliflozin and three related substances in spiked human plasma

“…The new pharmacological class of SGLT2-inhibitors lower blood glucose levels by targeting the kidney, reducing renal glucose reabsorption, and increasing urinary glucose elimination [2]. Determination of EMPA in bulk and/or pharmaceutical dosage forms as well as in human plasma has been reported in a few methods using spectrophotometric techniques [3, 4] and liquid chromatography [5–21]. Related substances are either produced as impurities from the manufacturing process, degradation products from improper storage or as metabolites that are either active, inactive or even toxic [22].…”

“…Figure 1 shows the chemical structure of EMPA and the related substances (ERS1–3). In spite of the many analytical techniques used for analysis of EMPA either alone [5–9] or in combination with other co-formulated drugs [10–18] and the available pharmacokinetic studies in literature [19–21], there are no analytical methods available with full details regarding plasma extraction and determination of EMPA and its three related substances in plasma samples to evaluate the pharmacokinetic parameters of the studied compounds. To the best of our knowledge, the present analysis is the first UPLC method carried out for the simultaneous determination of EMPA and these related substances in human plasma.…”

Liquid chromatographic and spectrofluorimetric assays of empagliflozin: Applied to degradation kinetic study and content uniformity testing

“…Enhancements of glycemic control and waist circumference provided further reasoning for use in patients with type 2 diabetes . According to the literature review (Tables and ), some spectrophotometric and chromatographic methods were developed for EGF assay in its pharmaceutical dosage form in addition to a review article discussing EGF assay in its different combinations…”