Elwira Telejko1. 1. Studium Kształcenia Podyplomowego, Białystok, Poland. ztpl@amb.edu.pl
Abstract
BACKGROUND: The efficacy of the angiotensin-converting enzyme (ACE) inhibitor perindopril in the treatment of hypertension, stable coronary artery disease, and heart failure is well established. The reduced stability of the current salt, perindopril-tert-butylamine, in extreme climatic conditions has prompted research into more stable compounds. This article presents stability and bioequivalence results for a new L-arginine salt of perindopril. METHODS: Drug stability studies were performed on nonsalified perindopril, perindopril-tert-butylamine, and perindopril arginine in closed and open containers. The bioequivalence of perindopril arginine was tested in 36 healthy male volunteers in an open-label, randomized, two-period, crossover pharmacokinetic study. A consumer study was carried out in 120 patients to assess preference for a simplified packaging using a high-density polyethylene canister designed for distribution to all climatic zones. RESULTS AND DISCUSSION: Perindopril arginine is 50% more stable than perindopril-tert-butylamine, which increases the shelf life from 2 to 3 years. At the revised dosage (perindopril arginine 5-10 mg/day corresponds to perindopril-tert-butylamine 4-8 mg/day), the new salt is equivalent in terms of pharmacokinetics, efficacy, safety, and acceptability. The consumer studies indicate a preference for the new packaging, with 62% of patients nominating the canister as better than the blister packs. CONCLUSION: The new perindopril arginine salt is equivalent to perindopril-tert-butylamine and more stable, and can be distributed to climatic zones III and IV without the need for specific packaging. The patient preference for the new packaging could have positive implications for compliance.
RCT Entities:
BACKGROUND: The efficacy of the angiotensin-converting enzyme (ACE) inhibitor perindopril in the treatment of hypertension, stable coronary artery disease, and heart failure is well established. The reduced stability of the current salt, perindopril-tert-butylamine, in extreme climatic conditions has prompted research into more stable compounds. This article presents stability and bioequivalence results for a new L-arginine salt of perindopril. METHODS: Drug stability studies were performed on nonsalified perindopril, perindopril-tert-butylamine, and perindopril arginine in closed and open containers. The bioequivalence of perindopril arginine was tested in 36 healthy male volunteers in an open-label, randomized, two-period, crossover pharmacokinetic study. A consumer study was carried out in 120 patients to assess preference for a simplified packaging using a high-density polyethylene canister designed for distribution to all climatic zones. RESULTS AND DISCUSSION: Perindopril arginine is 50% more stable than perindopril-tert-butylamine, which increases the shelf life from 2 to 3 years. At the revised dosage (perindopril arginine 5-10 mg/day corresponds to perindopril-tert-butylamine 4-8 mg/day), the new salt is equivalent in terms of pharmacokinetics, efficacy, safety, and acceptability. The consumer studies indicate a preference for the new packaging, with 62% of patients nominating the canister as better than the blister packs. CONCLUSION: The new perindopril arginine salt is equivalent to perindopril-tert-butylamine and more stable, and can be distributed to climatic zones III and IV without the need for specific packaging. The patient preference for the new packaging could have positive implications for compliance.