title: Bioequivalence of enalapril oral solution for treatment of pediatric hypertension and enalapril tablets.
abstract: Treating children with compounded liquid formulations of tablets intended for adults, where quality-control and compliance issues exist, was previously the only antihypertensive therapy option. A 1-mg/mL oral solution of enalapril maleate (enalapril), Epaned™, recently approved by the Food and Drug Administration (FDA), is the first angiotensin-converting enzyme inhibitor treatment for pediatric hypertension. The pharmacokinetic comparability of enalapril oral solution to the reference listed drug (RLD) tablet was assessed under fasted conditions. The effect of food on the bioavailability of enalapril oral solution was also assessed. Plasma levels of enalapril and the active metabolite, enalaprilat, were measured postdose using validated liquid chromatography-tandem mass spectroscopy methods. The ratio of enalapril oral solution to the RLD tablet was assessed. The 90% confidence intervals for the geometric mean ratios of Cmax , AUClast , and AUCinf for plasma levels of enalapril and enalaprilat were bioequivalent (within the FDA-accepted range of 80-125%). A commercially available oral solution of enalapril is bioequivalent to tablet formulations and can expand therapeutic options for pediatric patients. Administering enalapril oral solution with a high-fat meal decreased Cmax of plasma concentrations of enalapril and Cmax , AUClast , and AUCinf of plasma concentrations of enalaprilat compared to enalapril oral solution under fasting conditions.
authors.affiliation: Brady Moffett Consulting, Pearland, TX, USA.
authors.forename: Brady S
authors.initials: BS
authors.lastname: Moffett
authors.affiliation: ARD Pharmaceutical Consulting, Inc., Gobles, MI, USA.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: DiSanto
authors.affiliation: Bioanalytical Sciences, Worldwide Clinical Trials, Austin, TX, USA.
authors.forename: Orlando
authors.initials: O
authors.lastname: Espinosa
authors.affiliation: Bioanalytical Sciences, Worldwide Clinical Trials, Austin, TX, USA.
authors.forename: Jingguo
authors.initials: J
authors.lastname: Hou
authors.affiliation: Silvergate Pharmaceuticals, Inc., Greenwood Village, CO, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Colabuono
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects*; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004339:Drug Compounding; D016903:Drug Monitoring / Q000379:methods; D004656:Enalapril / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D019999:Pharmaceutical Solutions; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D019999:Pharmaceutical Solutions; D013607:Tablets; D004656:Enalapril
keywords: bioequivalence; enalapril; enalaprilat; hypertension; pediatric solution