A NEW ENALAPRIL MODIFIED RELEASE FORMULATION SHOWS COMPARABLE PHARMACODYNAMIC PROFILE TO THE REFERENCE DRUG IN HEALTHY SUBJECTS. PHASE I, PILOT STUDY

OTTAVIANO G; TUMARKIN M; OTERO-LOSADA M.; ROLDAN E; MULLER A; AZZATO F.; MILEI J.

Paris

Congreso; European Society of Hypertension ESH 2016 Annual Meeting; 2016

European Society of Hypertension

IntroductionThe aim of this study was to compare the pharmacodynamic profile of two new formulations of enalapril (modified release) with the standard reference drug.Design and MethodSix healthy volunteers, both sexes, participated in this single dose, open, randomized study using a cross-over design with treatment as a within-subjects factor. Each subject received 5 sequential treatments of enalapril maleate matching 5 formulation-dose combinations: Reference treatment (Renitec 20 mg, Merck & Co Inc), T1 (formulation A 20 mg), T2 (formulation B 20 mg), T3 (formulation A 10 mg), and T4 (formulation B 10 mg), with a 7-day washout period to achieve full drug clearance between consecutive treatments. Blood samples were obtained every 8 h for 24 h starting from the baseline (4 samples/subject) for determination of renin concentration, renin activity, and angiotensin convertase enzyme (ACE) activity. A 24-h ambulatory blood pressure monitoring was recorded. Results were submitted to ANOVA, expressed as mean ± SD for each treatment, and between-treatment comparison was performed using Bonferroni t test.ResultsTwenty-four hours after treatment, a 36% decrease in renin activity was observed in T1 compared with the reference treatment (ng/mL/h: 1.50±0.14 vs 2.37±0.24 respectively, p