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Concentration of Donepezil in the Cerebrospinal Fluid of AD Patients: Evaluation of Dosage Sufficiency in Standard Treatment Strategy
- Source :
- Neurotoxicity Research
- Publication Year :
- 2016
-
Abstract
- Although some studies have described the pharmacokinetics and pharmacodynamics of donepezil in the peripheral compartment, studies focused on drug transport across the blood–brain barrier are still very rare. To our knowledge, the fluctuation in the cerebrospinal fluid concentration of donepezil after administration of the drug has not been described in the literature so far. We recruited 16 patients regularly taking a standard therapeutic dose of donepezil (10 mg per day). All patients (Caucasian race) were treated for at least three months with a stable dose of 10 mg per day prior to sample collection. Patients were divided into two groups depending on the time of plasma and cerebrospinal fluid sampling: 12 h (n = 9; 4 M/5F aged 78.68 ± 7.35 years) and 24 h (n = 7; 3 M/4F aged 77.14 ± 5.87 years) after donepezil administration. The cerebrospinal fluid sample was collected by standard lumbar puncture technique using a single-use traumatic needle. The samples were analysed on an Agilent 1260 Series liquid chromatograph comprising a degasser, a quaternary pump, a light-tight autosampler unit set, a thermostated column compartment, and a UV/VIS detector. Agilent ChemStation software, the statistical software Prism4, version 5.0 (GraphPad Software, USA), and IBM® SPSS® Statistics were used for the analysis of the results. The difference in plasma concentration of donepezil after 12 h (mean ± SEM; 39.99 ± 5.90 ng/ml) and after 24 h (29.38 ± 1.71 ng/ml) was nonsignificant. In contrast, the donepezil concentration in the cerebrospinal fluid was significantly higher in the 24-h interval (7.54 ± 0.55 ng/ml) compared with the 12-h interval (5.19 ± 0.83 ng/ml, which is ~70 % based on mean cerebrospinal fluid values). Based on these data, it is plausible to predict that donepezil might produce a stronger AChE inhibition in the brain at 24 h compared with 12 h following the administration. This information may help physicians individually adjust the time of drug administration in the patients according to time course of the disease symptoms.
- Subjects :
- Male
Time Factors
Neuroscience(all)
Blood–brain barrier
Toxicology
030226 pharmacology & pharmacy
Spinal Puncture
Drug Administration Schedule
Article
Capillary Permeability
Clinical study
03 medical and health sciences
0302 clinical medicine
Cerebrospinal fluid
Pharmacokinetics
Piperidines
Alzheimer Disease
medicine
Humans
Donepezil
Nootropic Agents
Cholinesterase
Aged
Aged, 80 and over
biology
medicine.diagnostic_test
Dose-Response Relationship, Drug
Lumbar puncture
business.industry
General Neuroscience
Standard treatment
Middle Aged
medicine.anatomical_structure
Neurology
Blood-Brain Barrier
Anesthesia
Indans
biology.protein
Female
Sample collection
Neurology (clinical)
Cholinesterase Inhibitors
Cerebrospinal fluid concentrations
business
Alzheimer’s disease
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 14763524
- Volume :
- 31
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Neurotoxicity research
- Accession number :
- edsair.doi.dedup.....d671fdcd7335748a601ed96c68ea7bf6