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

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Neurotoxicity Research

ISSN

1029-8428

e-ISSN

—

Svazek periodika

31

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

162-168

Kód UT WoS článku

000392209200014

EID výsledku v databázi Scopus

2-s2.0-84990940870