title: Single-dose, 2-way crossover, bioequivalence study of two rosuvastatin formulations in normal healthy subjects under fasting conditions.
abstract: BACKGROUND
  Rosuvastatin, a synthetic lipid-lowering agent acts selectively by competitive inhibition of 3-hydroxy- 3-methylglutaryl-coenzyme A. It is indicated as an adjunct to diet in patients with hypercholesterolemia and mixed dyslipidemia.
  
  
  OBJECTIVE
  The purpose of this study was to demonstrate bioequivalence between a generic rosuvastatin 40 mg tablet (Zentiva, Prague, Czech Republic) and a reference product (Crestor, AstraZeneca, Luton, UK), under fasting conditions as required by the European Medicinal Agency.
  
  
  METHODS
  A single-oral 40 mg-dose, randomized, open-label, 2-way crossover design study was conducted in 42 healthy volunteers under fasting conditions. Rosuvastatin was administered following an overnight-fast in two occasions with a 14-day washout period in-between. Blood samples were collected in EDTA-K2 tubes prior to dosing and over a 96-hour period. Rosuvastatin was measured in plasma using an automated LC-MS/MS assay (range 81.02 - 40,512.00 pg/ml). Pharmacokinetics were performed using non-compartmental analyses approach to evaluate AUC(last), AUC∞ and C(max). ANOVA was performed on the ln-transformed data and the 90% Confidence Interval (CI) was determined. Bioequivalence will be concluded if the 90% CI falls within 80.00 - 125.00% for AUC(last) and C(max). Safety and tolerability were also evaluated.
  
  
  RESULTS
  39 volunteers completed the study and were considered for the pharmacokinetic and statistical analyses. Descriptive safety data analyses were performed on all subjects. All pharmacokinetic parameters met the acceptance criteria as the 90% CI were within 80.00 - 125.00%. Both formulations were well tolerated and no serious adverse events were reported.
  
  
  CONCLUSIONS
  This study showed that the test and reference products met the regulatory criteria for bioequivalence following a 40 mg oral dose under fasting conditions.
authors: PharmaNet Canada Inc, Montreal, Quebec, Canada.
authors: Fethi
authors: F
authors: Trabelsi
authors: Aleš
authors: A
authors: Bartůnek
authors: Raphaël
authors: R
authors: Vlavonou
authors: Lucie
authors: L
authors: Navrátilová
authors: Charlotte
authors: C
authors: Dubé
authors: Mario
authors: M
authors: Tanguay
authors: Tomáš
authors: T
authors: Hauser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D005215:Fasting; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium