The First Russian Fixed Combination of Indapamide Retard and Candesartan: Results of Two Pharmacokinetic and Bioequivalence Studies

Aim To study the pharmacokinetics and prove the bioequivalence of Hyposart I (indapamide 1.5 mg + candesartan 16 mg) modified-release film-coated tablets (OOO AKRIKHIN, Russia) compared to the concomitant drugs Arifon® retard (indapamide) prolonged-release film-coated tablets, 1.5 mg (Servier Laboratories, France) + Atacand® (candesartan) tablets, 16 mg (AstraZeneca AB, Sweden).Material and methods Two two-period crossover-design bioequivalence studies were conducted. In Study 1, healthy volunteers (n=72) took the drugs once either fasted or after a meal, and in Study 2 (n=24), they took them multiple times in a fasting condition. The dosing interval was 7 days. Analyte concentrations in samples were measured by a validated analytical method of high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Pharmacokinetic parameters were determined for both drugs in Study 1 and for indapamide only in Study 2.Results The 90% confidence intervals for the ratios of all Ln-transformed pharmacokinetic parameters (Cmax and AUC0-t of candesartan and indapamide in Study 1; Cmax, ss, AUC(0-τ) ss and Cτ, ss of indapamide in Study 2) were in the range of 80-125%.Conclusion The study has proved the bioequivalence of Hyposart I (AO AKRIKHIN) to the reference concomitant drugs Atacand® (AstraZeneca AB, Sweden) and Arifon® retard (Servier Laboratories, France).