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Bioequivalence evaluation of a triamterene–hydrochlorothiazide generic product: A new bioequivalence index for fixed-dose combinations

Regulatory Toxicology and Pharmacology
DOI: 10.1016/j.yrtph.2010.12.006
  • Fixed-Dose Combinations
  • Bioequivalence
  • Triamterene
  • Hydrochlorothiazide
  • Hplc-Uv
  • Liquid–Liquid Extraction
  • Design
  • Pharmacology


Abstract In this study, an open, double-blind, randomized, two-period, two-group crossover design was conducted in 14 healthy volunteers to study the bioequivalence of a fixed-dose generic product. After administration of test or reference products to each volunteer, both active ingredients were determined simultaneously in plasma samples using a developed and validated HPLC-UV method, and pharmacokinetic parameters, including Cmax, Tmax, AUC0–t, AUC0–∞, terminal elimination rate constant (λz), volume of distribution in steady state (Vd(ss)), mean residence time (MRT), clearance (Cl), terminal elimination rate constant (Kel) were determined in each subject using the standard non-compartmental approach. Statistical comparison showed that the test and reference products were bioequivalent in terms of both the rate and extent of bioavailability of both active ingredients. Finally, a new parameter named range overlap index (ROI) was introduced for the first time in this study in order to judge about the overall bioequivalence of the combination products. This parameter indicates the extent in which the two CI90% ranges of each parameter for two active ingredients overlap with each other. The ROI is suggested to be equal or more than 50% for two combination products in order to be known as bioequivalent. The ROI values of the bioequivalence-indicating parameters were 61.90%, 84.6%, and 76.0% for Cmax, AUC0→12, and AUC0→∞, respectively, which are indicative for bioequivalence in all the cases.

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