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

Reeves, S; Bertrand, J; D'Antonio, F; McLachlan, E; Nair, A; Brownings, S; Greaves, S; ... Howard, R; + view all (2016) A population approach to characterise amisulpride pharmacokinetics in older people and Alzheimer's disease. Psychopharmacology , 233 (18) pp. 3371-3381. 10.1007/s00213-016-4379-6. Green open access

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Abstract

Introduction 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. Methods 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. Results 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. Discussion 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.

Type: Article
Title: A population approach to characterise amisulpride pharmacokinetics in older people and Alzheimer's disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s00213-016-4379-6
Publisher version: http://dx.doi.org/10.1007/s00213-016-4379-6
Language: English
Additional information: © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Pharmacology & Pharmacy, Psychiatry, Neurosciences & Neurology, Amisulpride, Elderly, Alzheimer's disease, Age, Population pharmacokinetics, Antipsychotic, ORGANIC CATION TRANSPORTERS, ANTIPSYCHOTIC-DRUGS, SCHIZOAFFECTIVE DISORDER, CONSENSUS GUIDELINES, RECEPTOR OCCUPANCY, PLASMA AMISULPRIDE, DEMENTIA, SCHIZOPHRENIA, UPDATE, PHARMACODYNAMICS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/1509337
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