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

Sci Rep. 2017 May 31;7(1):2583. doi: 10.1038/s41598-017-02895-7.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Benzhydryl Compounds / administration & dosage*
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / blood
  • Benzhydryl Compounds / pharmacokinetics
  • Blood Glucose
  • Chromatography, High Pressure Liquid
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / pathology
  • Dose-Response Relationship, Drug
  • Egypt
  • Ethnicity
  • Glucosides / administration & dosage*
  • Glucosides / adverse effects
  • Glucosides / blood
  • Glucosides / pharmacokinetics
  • Healthy Volunteers
  • Humans
  • Male
  • Sodium-Glucose Transporter 2 Inhibitors / administration & dosage*
  • Sodium-Glucose Transporter 2 Inhibitors / blood
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology
  • Tandem Mass Spectrometry

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Sodium-Glucose Transporter 2 Inhibitors
  • empagliflozin