Relative Bioavailability of Enalapril Administered as Orodispersible Minitablets in Healthy Adults

The angiotensin‐converting enzyme inhibitor enalapril is commonly used to treat chronic heart failure in children. Because some children are unable to swallow capsules or tablets, a new, age‐appropriate, orodispersible minitablet (ODMT) containing 1 mg of enalapril was developed within the EU‐funded LENA (Labeling of Enalapril from Neonates up to Adolescents) consortium. In order to support the clinical evaluation of this new formulation in children, a relative bioavailability study was performed in healthy adults, comparing the bioavailability of enalapril in the ODMT with that of a reference product (RP) Renitec, a registered standard enalapril tablet formulation. In this open‐label, randomized 3‐way crossover study, 24 healthy subjects received a 10‐mg enalapril dose administered as (1) 2 × 5‐mg tablets of the RP swallowed with water, (2) 10 × 1‐mg ODMT swallowed with water, and (3) 10 × 1 mg ODMT dispersed on the tongue. When the relative bioavailability of the ODMT formulation swallowed with water was compared with that of the RP, the estimated 90%CIs for the ratio of area under the concentration‐time curve (AUC 0‐∞ ) and or peak concentration (C max ) of enalapril were 92.34% to 106.49% and 91.28% to 115.72%, respectively, which are within the accepted bioequivalence limits of 80% to 125%. Following dispersion of the ODMT in the mouth, a slightly higher C max for enalapril was observed as compared with the RP with an upper 90%CI of 127.57%, slightly exceeding the bioequivalence limit. Taken together, it was demonstrated that the method of administration of the ODMT, swallowed or dispersed, did not significantly affect the bioavailability of enalapril.