Relative Bioavailability of Enalapril Administered as Orodispersible Minitablets in Healthy Adults.

Autor: Van Hecken A; Center for Clinical Pharmacology, University Hospitals of Leuven, Leuven, Belgium., Burckhardt BB; Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich Heine University, Düsseldorf, Germany., Khalil F; Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich Heine University, Düsseldorf, Germany., de Hoon J; Center for Clinical Pharmacology, University Hospitals of Leuven, Leuven, Belgium., Klingmann I; Pharmaplex bvba, Wezembeek-Oppem, Belgium., Herbots M; Center for Clinical Pharmacology, University Hospitals of Leuven, Leuven, Belgium., Laeer S; Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich Heine University, Düsseldorf, Germany., Lagler FB; Paracelsus Medical University, Salzburg, Austria., Breitkreutz J; Ethicare GmbH, Haltern am See, Germany.
Jazyk: angličtina
Zdroj: Clinical pharmacology in drug development [Clin Pharmacol Drug Dev] 2020 Feb; Vol. 9 (2), pp. 203-213. Date of Electronic Publication: 2019 Aug 14.
DOI: 10.1002/cpdd.728
Abstrakt: 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.
(© 2019, The American College of Clinical Pharmacology.)
Databáze: MEDLINE
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