Model-based evaluation of the impact of formulation and food intake on the complex oral absorption of mavoglurant in healthy subjects.

Research output: Contribution to journalArticle

  • External authors:
  • Thierry Wendling
  • Etienne Pigeolet
  • Swati Dumitras
  • Ralph Woessner

Abstract

PURPOSE: To compare the pharmacokinetics of intravenous (IV), oral immediate-release (IR) and oral modified-release (MR) formulations of mavoglurant in healthy subjects, and to assess the food effect on the MR formulation's input characteristics. METHODS: Plasma concentration-time data from two clinical studies in healthy volunteers were pooled and analysed using NONMEM®. Drug entry into the systemic circulation was modelled using a sum of inverse Gaussian (IG) functions as an input rate function, which was estimated specifically for each formulation and food state. RESULTS: Mavoglurant pharmacokinetics was best described by a two-compartment model with a sum of either two or three IG functions as input function. The mean absolute bioavailability from the MR formulation (0.387) was less than from the IR formulation (0.436). The MR formulation pharmacokinetics were significantly impacted by food: bioavailability was higher (0.508) and the input process was shorter (complete in approximately 36 versus 12 h for the fasted and fed states, respectively). CONCLUSIONS: Modelling and simulation of mavoglurant pharmacokinetics indicate that the MR formulation might provide a slightly lower steady-state concentration range with lower peaks (possibly better drug tolerance) than the IR formulation, and that the MR formulation's input properties strongly depend on the food conditions at drug administration.

Bibliographical metadata

Original languageEnglish
Pages (from-to)1764-1778
Number of pages14
JournalPharmaceutical Research
Volume32
Issue number5
DOIs
Publication statusPublished - May 2015

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