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Concentration of donepezil in the cerebrospinal fluid of AD patients: evaluation of dosage sufficiency in standard treatment strategy

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F17%3A43875723" target="_blank" >RIV/60162694:G44__/17:43875723 - isvavai.cz</a>

  • Alternative codes found

    RIV/00159816:_____/17:00065642 RIV/00216208:11130/17:10332522 RIV/00216208:11150/17:10332522 RIV/00179906:_____/17:10332522 RIV/00064203:_____/17:10332522

  • Result on the web

    <a href="http://link.springer.com/article/10.1007%2Fs12640-016-9672-y" target="_blank" >http://link.springer.com/article/10.1007%2Fs12640-016-9672-y</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1007/s12640-016-9672-y" target="_blank" >10.1007/s12640-016-9672-y</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Concentration of donepezil in the cerebrospinal fluid of AD patients: evaluation of dosage sufficiency in standard treatment strategy

  • Original language description

    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 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 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 IBMA (R) SPSSA (R) 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 similar to 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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30103 - Neurosciences (including psychophysiology)

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2017

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Neurotoxicity Research

  • ISSN

    1029-8428

  • e-ISSN

  • Volume of the periodical

    31

  • Issue of the periodical within the volume

    1

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    7

  • Pages from-to

    162-168

  • UT code for WoS article

    000392209200014

  • EID of the result in the Scopus database

    2-s2.0-84990940870