Publication: Clinical and Translational Science
Abstract
Generic and brand-name extended-release metoprolol tablets may differ in time-to-peak-concentration despite comparable overall exposure, raising questions about therapeutic equivalence across the full dosing interval. This randomized crossover trial in adults with hypertension compared pharmacokinetics and pharmacodynamics (heart rate, blood pressure, heart rate variability) of brand-name metoprolol extended-release tablets against two generic formulations, with pharmacokinetic parameters calculated using Phoenix WinNonlin. While AUC and Cmax were similar across products, time to maximum concentration differed significantly between the brand and each generic, and heart rate variability was more sustained over time for the brand-name product than one generic. These differences in absorption timing between metoprolol extended-release products may have implications for their effects on autonomic balance across the dosing interval.
Author(s): Mosley SA, Kim S, El Rouby N, Lingineni K, Esteban VV, Gong Y, Chen Y, Estores D, Feng K, Kim H, Kinjo M, Langaee T, Li Z, Schmidt SOF, Johnson JA, Frye RF, Fang LL, Zhao L, Binkley PF, Schmidt S, Cavallari LH
Published: May 21, 2022
Phoenix NLME: Linking PK to Cardiovascular Effect
Phoenix NLME’s modeling connected metoprolol pharmacokinetics to heart rate and blood pressure effects in this crossover study comparing brand and generic formulations. Phoenix NLME is also available through RsNLME, bringing population PK/PD modeling into R for teams who prefer that environment, within a Phoenix platform used by more than 1,600 companies across 60 countries.
