title: Study on the bioequivalence of two formulations of eplerenone in healthy volunteers under fasting conditions: data from a single-center, randomized, single-dose, open-label, 2-way crossover bioequivalence study.
abstract: BACKGROUND
  Eplerenone (CAS 107724-20-9) prevents the binding of aldosterone, a key hormone in the renin-angiotensin-aldosterone-system (RAAS), which is involved in the regulation of blood pressure and the pathophysiology of cardiovascular disease and is indicated, in addition to standard therapy including beta-blockers, to reduce the risk of cardiovascular mortality and morbidity in stable patients with left ventricular dysfunction (LVEF < or = 40%) and clinical evidence of heart failure after recent myocardial infarction.
  
  
  OBJECTIVE
  The aim of this study was to assess the bioequivalence of a new eplerenone 50 mg formulation (test formulation) vs. the reference product, as required by European regulatory authorities for the marketing of a generic product.
  
  
  METHODS
  This was a single-center, randomized, single-dose, open-label, 2-way crossover study in healthy volunteers under fasting conditions. Plasma samples were collected up to 24 h post-dosing and plasma eplerenone levels were determined by reversed phase high performance liquid chromatography and by tandem mass spectrometry detection (ie, the LC-MS/MS method). Pharmacokinetic parameters were calculated using non-compartmental analysis. Area under the concentration-time curve from time zero to time of last non-zero concentration (AUClast) and maximum observed concentration (Cmax) were the main evaluation criteria. All of the above-mentioned pharmacokinetic parameters were analyzed using 90% geometric confidence interval of the ratio (T/R) of least-squares means from the ANOVA of the 1n-transformed parameter. Tolerability was monitored using physical examination, including vital sign measurements and laboratory analysis.
  
  
  RESULTS
  According to the classical approach, the 90% geometric confidence intervals obtained by analysis of variance for AUClast and Cmax were within the predefined ranges (80.00-125.00%).
  
  
  CONCLUSIONS
  Bioequivalence between test and reference formulations, both in terms of rate and extension of absorption, under fasting conditions was concluded according to European guidelines. Both formulations were well tolerated.
authors.affiliation: Medical Department, Grupo Tecnimede, Sociedade Tecnico-Medicinal S.A. Zona Industrial da Abrunheira, R. da Tapada Grande, no. 2, Abrunheira, 2710-089 Sintra, Portugal. dmed.ct@tecnimede.pt
authors.forename: Susana
authors.initials: S
authors.lastname: Almeida
authors.forename: Pedro
authors.initials: P
authors.lastname: Pedroso
authors.forename: Augusto
authors.initials: A
authors.lastname: Filipe
authors.forename: Catarina
authors.initials: C
authors.lastname: Pinho
authors.forename: Rita
authors.initials: R
authors.lastname: Neves
authors.forename: Cintia
authors.initials: C
authors.lastname: Jiménez
authors.forename: Eric
authors.initials: E
authors.lastname: Sicard
authors.forename: Marc
authors.initials: M
authors.lastname: Lefebvre
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D000077545:Eplerenone; D005215:Fasting; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics*; D013148:Spironolactone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone