A population approach to characterise amisulpride pharmacokinetics in older people and Alzheimer's disease

作者：Reeves Suzanne^*; Bertrand Julie; D'Antonio Fabrizia; McLachlan Emma; Nair Akshay; Brownings Stuart; Greaves Suki; Smith Alan; Taylor David; Howard Robert

来源：Psychopharmacology, 2016, 233(18): 3371-3381.

DOI：10.1007/s00213-016-4379-6

• Amisulpride
• Elderly
• Alzheimer's disease
• Age
• Population pharmacokinetics
• Antipsychotic

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.

• 出版日期2016-9