title: The advantages of combination therapy on hypertension: development of immediate release perindopril-indapamide tablet and assessment of bioequivalence studies.
abstract: 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 4/1.25 mg Tablet-S.A.Servier Benelux N.V.) and test (Convers Plus 4/1.25 mg Tablet-ARGESAN Pharmaceutical Company) tablets have been found bioequivalent. The results of pharmacokinetic parameters for perindopril, perindoprilat and indapamide were found as Cmax = 23.179 µg/mL, tmax = 0.729 h, t1/2 = 1.429 h; AUC0-t = 26.998 µgs/mL, AUC0-inf = 27.117 µgs/mL; Cmax = 1.834 µg/mL, tmax = 8.792 h, t1/2 = 40.699 h; AUC0-t = 54.828 µgs/mL, AUC0-inf = 77.113 µgs/mL; Cmax = 18.994 µg/mL, tmax = 3.417 h, t1/2 = 16.626 h and AUC0-t = 385.829 µgs/mL, AUC0-inf = 410.728 µgs/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 Cmax, in 90% confidence limits.
authors.affiliation: a Argis Pharmaceuticals Inc. Co. , Ankara , Turkey and.
authors.forename: A
authors.initials: A
authors.lastname: Ölçer
authors.affiliation: a Argis Pharmaceuticals Inc. Co. , Ankara , Turkey and.
authors.forename: M
authors.initials: M
authors.lastname: Ölçer
authors.affiliation: b Center for Drug R&D and Pharmacokinetic Applications, Ege University , Bornova , Izmir , Turkey.
authors.forename: I
authors.initials: I
authors.lastname: İnce
authors.affiliation: b Center for Drug R&D and Pharmacokinetic Applications, Ege University , Bornova , Izmir , Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Karasulu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018592:Cross-Over Studies; D004338:Drug Combinations; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007190:Indapamide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000627:therapeutic use*; D013607:Tablets / Q000627:therapeutic use*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004338:Drug Combinations; D013607:Tablets; C494243:indapamide, perindopril drug combination; D007190:Indapamide; D020913:Perindopril
keywords: Bioequivalence; dissolution; hypertension; immediate release tablet; indapamide; perindopril erbumine; single pill drug combinations