title: A population approach to characterise amisulpride pharmacokinetics in older people and Alzheimer's disease.
abstract: Current prescribing guidelines for the antipsychotic amisulpride are based largely on pharmacokinetic (PK) studies in young adults, and there is a relative absence of data on older patients, who are at greatest risk of developing adverse events.
  
  
  
  This study aimed to develop a population PK model for amisulpride specifically in older people, by combining data from a richly sampled phase 1, single (50 mg) dose study in healthy older people (n = 20, 65-79 years), with a clinical dataset obtained during off label, low-dose (25-75 mg daily) amisulpride prescribing in older people with Alzheimer's disease (AD) (n = 25, 69-92 years), as part of an observational study.
  
  
  
  After introducing a scaling factor based on body weight, age accounted for 20 % of the inter-individual variability in drug clearance (CL), resulting in a 54 % difference in CL between those aged 65 and those aged 85 years, and higher blood concentrations in older patients.
  
  
  
  These findings argue for the consideration of age and weight-based dose stratification to optimise amisulpride prescribing in older people, particularly in those aged 85 years and above.
authors.affiliation: Division of Psychiatry, University College London, London, W1T7NF, UK. suzanne.reeves@ucl.ac.uk.|Department of Old Age Psychiatry, Kings College London, London, UK. suzanne.reeves@ucl.ac.uk.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Reeves
authors.affiliation: UMR 1137 IAME INSERM University Paris 7, France and Genetics Institute, University College London, London, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Bertrand
authors.affiliation: Division of Psychiatry, University College London, London, W1T7NF, UK.|Department of Old Age Psychiatry, Kings College London, London, UK.
authors.forename: Fabrizia
authors.initials: F
authors.lastname: D'Antonio
authors.affiliation: Department of Old Age Psychiatry, Kings College London, London, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: McLachlan
authors.affiliation: Division of Psychiatry, University College London, London, W1T7NF, UK.
authors.forename: Akshay
authors.initials: A
authors.lastname: Nair
authors.affiliation: Department of Old Age Psychiatry, Kings College London, London, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Brownings
authors.affiliation: South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: Suki
authors.initials: S
authors.lastname: Greaves
authors.affiliation: South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Smith
authors.affiliation: South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Taylor
authors.affiliation: Division of Psychiatry, University College London, London, W1T7NF, UK.|Department of Old Age Psychiatry, Kings College London, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Howard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D013469:Sulpiride; D000077582:Amisulpride
keywords: Age; Alzheimer’s disease; Amisulpride; Antipsychotic; Elderly; Population pharmacokinetics