Pharmacokinetic/Pharmacodynamic modeling and simulation of the effect of medications on β-amyloid aggregates and cholinergic neurocycle
| Autor: | Said S.E.H. Elnashaie, Ibrahim Mustafa, Ali Elkamel, Asmaa A. R. Awad, Hedia Fgaier |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Pharmacokinetic pharmacodynamic
020209 energy General Chemical Engineering 02 engineering and technology Pharmacology Computer Science Applications chemistry.chemical_compound 020401 chemical engineering chemistry β amyloid Postsynaptic potential Pharmacodynamics 0202 electrical engineering electronic engineering information engineering Galantamine medicine Choline Cholinergic 0204 chemical engineering Acetylcholine medicine.drug |
| Zdroj: | Computers & Chemical Engineering. 126:231-240 |
| ISSN: | 0098-1354 |
| DOI: | 10.1016/j.compchemeng.2019.04.017 |
| Popis: | In this paper, a 10th order nonlinear pharmacokinetics/pharmacodynamics (PK/PD) model was developed to evaluate the impact of Alzheimer's disease (AD) medications such as galantamine on β-amyloid (βA) aggregates and levels of acetylcholine (ACh) and choline in the presynaptic (compartment 1) and postsynaptic (compartment 2) neurons based on the choline leakage hypothesis. The development is performed by incorporating a one-compartment PD/PK model into the two-enzyme/two-compartment model built by Mustafa et al., (2012a,b). The interaction between medications and βA aggregates is formulated based on a 6-h single oral dose of 2.5-10 mg of drugs which indicated PK/PD changes similar to the experimental findings obtained by Goh et al., (2011). Enhanced cholinergic behavior was observed in terms of a reduction in βA aggregates’ concentrations and increase in the levels of ACh and choline in the pre-synaptic and postsynaptic neurons. The results indicate that therapeutic and pharmacological agents inhibiting βA aggregation represent a likely successful approach to develop future trials, new diagnostic techniques, and medications for AD. This study is helpful in developing experimental animal models to support the development of AD medications. |
| Databáze: | OpenAIRE |
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