The advantages of combination therapy on hypertension: development of immediate release perindopril-indapamide tablet and assessment of bioequivalence studies


OLCER A., OLCER M., İNCE İ. , KARASULU E.

PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY, cilt.21, ss.239-249, 2016 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 21 Konu: 2
  • Basım Tarihi: 2016
  • Doi Numarası: 10.3109/10837450.2014.991878
  • Dergi Adı: PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
  • Sayfa Sayısı: ss.239-249

Özet

Hypertension has a major associated risk for organ damage and mortality, which is further heightened in patients with prior cardiovascular events, comorbid diabetes mellitus, microalbuminuria and renal impairment. Convers Plus tablet including perindopril erbumine (PE), which is an angiotensin converting enzyme (ACE) inhibitor, and indapamide, which is diuretic, was designed as a combined tablet to succes in the treatment of hypertension. Physico-pharmaceutical properties and characterization studies were evaluated in vitro conditions. Later on in vivo study was planned as a cross-designed, randomized, open-labeled, single-dose, single-center study via peroral route in 24 healthy male subjects. In this study, bioequivalence with primary pharmacokinetical target parameters reference (Bipreterax 4/1.25mg Tablet-S.A.Servier Benelux N.V.) and test (Convers Plus 4/1.25mg Tablet-ARGESAN Pharmaceutical Company) tablets have been found bioequivalent. The results of pharmacokinetic parameters for perindopril, perindoprilat and indapamide were found as C-max=23.179 mu g/mL, t(max)=0.729h, t(1/2)=1.429h; AUC(0-t)=26.998 mu gs/mL, AUC(0-inf)=27.117 mu gs/mL; C-max=1.834 mu g/mL, t(max)=8.792h, t(1/2)=40.699h; AUC(0-t)=54.828 mu gs/mL, AUC(0-inf)=77.113 mu gs/mL; C-max=18.994 mu g/mL, t(max)=3.417h, t(1/2)=16.626h and AUC(0-t)=385.829 mu gs/mL, AUC(0-inf)=410.728 mu gs/mL respectively. In conclusion, physico-pharmaceutical properties and results of clinical trials show that Convers Plus tablets have been found as bioequivalent for perindopril, perindoprilat and indapamide in terms of AUC and C-max, in 90% confidence limits.