Estimation of plasma IC50 of donepezil for cerebral acetylcholinesterase inhibition in patients with Alzheimer disease using positron emission tomography

Clinical Neuropharmacology
Tsuneyoshi OtaToshiaki Irie

Abstract

Estimate the value of in vivo plasma IC50 of donepezil, the concentration of donepezil in plasma that inhibits brain acetylcholinesterase (AChE) activity by 50% at the steady-state conditions of donepezil between the plasma and the brain. N-[C] methylpiperidin-4-yl acetate ([C]MP4A) positron emission tomography was performed in 16 patients with probable Alzheimer disease (AD) before and during the treatment of donepezil (5 mg/day) with a mean interval of 5.3 months. The plasma IC50 value of donepezil was estimated from plasma donepezil concentrations and cerebral cortical mean AChE inhibition rates measured by positron emission tomography, using one-parameter model. Donepezil reduced AChE activity uniformly in the cerebral cortex compared with the baseline in each AD patient, and the mean reduction rate in the cerebral cortex was 34.6%. The donepezil concentrations in the plasma ranged from 18.5 to 43.9 ng/mL with a mean of 28.9 +/- 7.3 ng/mL. The plasma IC50 value was estimated to be 53.6 +/- 4.0 ng/mL. Once the plasma IC50 of donepezil is determined, the brain AChE inhibition rate could be estimated from the plasma concentration of donepezil in each subject based on the plasma IC50. Now that the mean donepezil concentrations ...Continue Reading

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Citations

Jul 31, 2012·International Journal of Endocrinology·Piotr KocełakMagdalena Olszanecka-Glinianowicz
May 3, 2014·Expert Opinion on Drug Metabolism & Toxicology·David Prvulovic, Barbara Schneider
Jun 21, 2012·Psychogeriatrics : the Official Journal of the Japanese Psychogeriatric Society·Takaaki MoriTetsuya Suhara
Apr 1, 2011·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Mizuho SekineTetsuya Suhara
Feb 16, 2010·Neuropharmacology·Jaegyu HwangKyoungho Suk
Nov 11, 2014·Therapeutic Drug Monitoring·Gudrun HefnerAndreas Fellgiebel
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Oct 27, 2017·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Drew R DeBaySultan Darvesh
Sep 27, 2019·Experimental and Therapeutic Medicine·Mai HazekawaManabu Nakashima

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