In this study, the in vitro and in vivo interchangeability between generic candesartan 16 mg and the branded formulation was assessed. The in vitro release of these products was conducted in 3 pH media (1.2, 5.0, and 6.8), and similarity factors (f₂) were calculated. This bioequivalence study was a randomized, 2-period crossover study that included 42 healthy adult male subjects under fasting conditions with a 9-day washout. The pharmacokinetic (PK) parameters AUC_0-last, AUC_0-∞, and C_max, t_max, and the elimination half-life time were assessed based on the plasma concentrations of candesartan, using a newly developed and validated liquid chromatography-tandem mass spectrometry bioanalytical method with acceptable degrees of linearity, sensitivity, precision, and accuracy. The geometric mean (ng·h/mL) of the AUC_0-∞ for the test and brand was 1595.49 and 1620.54, respectively, and the C_max (ng/mL) was 160.91 and 160.88, respectively. The 90%CIs of geometric mean ratios (test-to-reference ratios) were 98.26%, 98.45%, and 99.86% for AUC_0-last, AUC_0-∞, and C_maxrespectively. These PK parameters lie within the US Food and Drug Administration– and European Medicines Agency–specified bioequivalence limit (80%-125%). Both products were well tolerated by all the subjects. The tested drug product was bioequivalent to the reference drug and had the same safety profile. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology

Title

Clinical Pharmacology in Drug Development

Publisher

Blackwell Publishing Ltd

Publisher Country

United States of America

Indexing

Thomson Reuters

Impact Factor

1.375

Publication Type

Prtinted only

Volume

7

Year

2018

Pages

621-626