title: Model-based evaluation of the impact of formulation and food intake on the complex oral absorption of mavoglurant in healthy subjects.
abstract: OBJECTIVE
  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.
authors.affiliation: Manchester Pharmacy School, The University of Manchester, Manchester, UK.
authors.forename: Thierry
authors.initials: T
authors.lastname: Wendling
authors.forename: Kayode
authors.initials: K
authors.lastname: Ogungbenro
authors.forename: Etienne
authors.initials: E
authors.lastname: Pigeolet
authors.forename: Swati
authors.initials: S
authors.lastname: Dumitras
authors.forename: Ralph
authors.initials: R
authors.lastname: Woessner
authors.forename: Leon
authors.initials: L
authors.lastname: Aarons
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D003198:Computer Simulation; D004435:Eating; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D007211:Indoles; D064529:Receptor, Metabotropic Glutamate 5; C581397:mavoglurant