Mixed-effect circadian rhythm model for human erythrocyte acetylcholinesterase activity-application to the proof of concept of cholinesterase inhibition by acorn extract in healthy subjects with galantamine as positive control.
Purpose: The aim of this study was to develop a non-linear mixed effect circadian rhythm model of acetylcholinesterase (AChE) activity variation and to evaluate the inhibitory effect of acorn extract (2 g) and galantamine (16 mg), used as positive control, on human AChE in red blood cells (RBC). Met...
| Published in: | European Journal of Clinical Pharmacology Vol. 68; no. 5; pp. 599 - 606 |
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| Main Authors: | , , , , |
| Format: | equations & formulas research tables/charts randomized controlled trial Journal Article |
| Published: |
Springer Nature
May2012
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104555227&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104555227 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: May2012 vid: 68 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104555227 74466798 10.1007/s00228-011-1192-3 NLM22207414 104555227 ppf: 599 ppct: 7 formats: fmt: @attributes: type: P tig: atl: Mixed-effect circadian rhythm model for human erythrocyte acetylcholinesterase activity-application to the proof of concept of cholinesterase inhibition by acorn extract in healthy subjects with galantamine as positive control. aug: au: Han, Seunghoon Lee, Jongtae Jeon, Sangil Hong, Taegon Yim, Dong-Seok sug: subj: Acetylcholinesterase Blood Cholinesterase Inhibitors Galanthamine Administration and Dosage Circadian Rhythm Alzheimer's Disease Drug Therapy Dementia Drug Therapy Plant Extracts Therapeutic Use Human Models, Statistical Randomized Controlled Trials Random Assignment Crossover Design Male Adult Middle Age South Korea Plant Extracts Administration and Dosage Time Factors Confidence Intervals Descriptive Statistics T-Tests Funding Source Adult: 19-44 years Middle Aged: 45-64 years Male ab: Purpose: The aim of this study was to develop a non-linear mixed effect circadian rhythm model of acetylcholinesterase (AChE) activity variation and to evaluate the inhibitory effect of acorn extract (2 g) and galantamine (16 mg), used as positive control, on human AChE in red blood cells (RBC). Methods: This was an open-label, randomized, three-way crossover study involving 12 healthy subjects who received one of the treatments in each study period: no treatment, acorn extract, and galantamine. RBC AChE activity was measured in peripheral blood samples collected at 0 (pre-dose), 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16 and 24 h post-dose administration. Non-linear mixed effect modeling was performed using NONMEM (ver. 7.0). Results: The circadian variation of AChE activity was best described using two mixed effect cosine functions, with periods of 24 and 12 h, respectively. When the inhibitory effect terms were added, the model was significantly improved for both acorn extract and galantamine. In terms of the effect, a 2-g single dose of acorn extract showed AChE inhibition (about 5%) similar to that of a 16-mg single dose of galantamine, in the first 24 h after administration. Conclusions: Based on the very pronounced inter- and intra-day variation in AChE activity in RBC, we conclude that the model-based approach is essential for the proof of concept and quantitation of AChE inhibition in human subjects. pubtype: Academic Journal doctype: equations & formulas research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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