Donepezil and Rivastigmine: Pharmacokinetic profile and brain-targeting after intramuscular administration in rats

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F20%3A10418655" target="_blank" >RIV/00179906:_____/20:10418655 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/20:00556478 RIV/62690094:18470/20:50017372

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=sN3bePFaQU" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=sN3bePFaQU</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.22037/ijpr.2019.1100723" target="_blank" >10.22037/ijpr.2019.1100723</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Donepezil and Rivastigmine: Pharmacokinetic profile and brain-targeting after intramuscular administration in rats

Popis výsledku v původním jazyce

Current palliative pharmacotherapy of Alzheimer&apos;s disease based on the cholinergic hypothesis led to the development of four cholinesterase inhibitors. These compounds can bring prolongation of the symptom-free period in some patients. This is the first report directly comparing donepezil and rivastigmine plasma and brain levels in in-vivo study. Donepezil and rivastigmine were applied i.m. to rats; the dose was calculated from clinical recommendations. The samples were analysed on an Agilent 1260 Series LC with UV/VIS detector. An analytical column (Waters Spherisorb S5 W (250 mm x 4.6 i.d.; 5 mu m particle size)) with guard column (Waters Spherisorb S5 W (30 mm x 4.6 mm i.d.)) was used. The mobile phase contained acetonitrile and 50 mM sodium dihydrogen phosphate (17:83; v/v); pH 3.1. The LLOQ in rat plasma was 0.5 ng/mL for donepezil and 0.8 ng/mL for rivastigmine, and the LLOQ in rat brain was 1.0 ng/mL for donepezil and 1.1 ng/mL for rivastigmine. Both compounds showed ability to target the central nervous system, with brain concentrations exceeding those in plasma. Maximum brain concentration after i.m. administration was reached in the 36 (8.34 +/- 0.34 ng/mL) and 17 minute (6.18 +/- 0.40 ng/mL), respectively for donepezil and rivastigmine. The differences in brain profile can be most easily expressed by plasma/brain AUCtotal ratios: donepezil ratio in the brain was nine-times higher than in plasma and rivastigmine ratio was less than two-times higher than in plasma.

Název v anglickém jazyce

Donepezil and Rivastigmine: Pharmacokinetic profile and brain-targeting after intramuscular administration in rats

Popis výsledku anglicky

Current palliative pharmacotherapy of Alzheimer&apos;s disease based on the cholinergic hypothesis led to the development of four cholinesterase inhibitors. These compounds can bring prolongation of the symptom-free period in some patients. This is the first report directly comparing donepezil and rivastigmine plasma and brain levels in in-vivo study. Donepezil and rivastigmine were applied i.m. to rats; the dose was calculated from clinical recommendations. The samples were analysed on an Agilent 1260 Series LC with UV/VIS detector. An analytical column (Waters Spherisorb S5 W (250 mm x 4.6 i.d.; 5 mu m particle size)) with guard column (Waters Spherisorb S5 W (30 mm x 4.6 mm i.d.)) was used. The mobile phase contained acetonitrile and 50 mM sodium dihydrogen phosphate (17:83; v/v); pH 3.1. The LLOQ in rat plasma was 0.5 ng/mL for donepezil and 0.8 ng/mL for rivastigmine, and the LLOQ in rat brain was 1.0 ng/mL for donepezil and 1.1 ng/mL for rivastigmine. Both compounds showed ability to target the central nervous system, with brain concentrations exceeding those in plasma. Maximum brain concentration after i.m. administration was reached in the 36 (8.34 +/- 0.34 ng/mL) and 17 minute (6.18 +/- 0.40 ng/mL), respectively for donepezil and rivastigmine. The differences in brain profile can be most easily expressed by plasma/brain AUCtotal ratios: donepezil ratio in the brain was nine-times higher than in plasma and rivastigmine ratio was less than two-times higher than in plasma.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GA18-13283S" target="_blank" >GA18-13283S: Vliv experimentálního gastrointestinálního poškození na farmakokinetiku léčiv Alzheimerovy choroby</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Iranian Journal of Pharmaceutical Research

ISSN

1735-0328

e-ISSN

—

Svazek periodika

19

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

IR - Íránská islámská republika

Počet stran výsledku

8

Strana od-do

95-102

Kód UT WoS článku

000591175000010

EID výsledku v databázi Scopus

2-s2.0-85096089544