- MeSH
- biologický transport MeSH
- hematoencefalická bariéra metabolismus MeSH
- indany * krev chemie farmakokinetika MeSH
- krysa rodu rattus MeSH
- lineární modely MeSH
- piperidiny * krev chemie farmakokinetika MeSH
- potkani Wistar MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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.
- MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- časové faktory MeSH
- cholinesterasové inhibitory krev farmakokinetika terapeutické užití MeSH
- hematoencefalická bariéra MeSH
- indany krev farmakokinetika terapeutické užití MeSH
- kapilární permeabilita MeSH
- lidé středního věku MeSH
- lidé MeSH
- nootropní látky krev farmakokinetika terapeutické užití MeSH
- piperidiny krev farmakokinetika terapeutické užití MeSH
- rozvrh dávkování léků MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinální punkce MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
A simple, rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated for the quantitative determination in rat plasma of a new candidate for AD treatment, namely PC 48 (a 7-MEOTA-donepezil like compound) in rat plasma. Sample preparation involved pH adjustment with sodium hydroxide followed by solvent extraction with ethyl acetate:dichloromethane (80:20, v/v). The chromatographic separation was achieved on an Ascentis Express RP-Amide column (75 mm × 2.1mm, 2.7 μm) with a gradient mobile phase consisting of 0.05 M aqueous formic acid and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry on an LTQ XL system using the MS/MS CID (collision-induced dissociation) mode. The method was linear in the range 0.1-1000 ng/ml (r(2)=0.999) with a lower limit of quantitation of 0.1 ng/mL. Extraction recovery was in the range 63.5-72.1% for PC 48 and 70.5% for reserpine (internal standard, IS). Intra- and inter-day precisions measured as relative standard deviation were below 10.8% and accuracy was from -7.2% to 7.4%. The method was successfully applied to a pharmacokinetic study involving intramuscular application of 3.86 mg/kg PC 48 to rats for the first time. Pharmacokinetic parameters for PC 48 include Cmax 39.09 ± 4.45 ng/mL,Tmax 5.00 ± 3.08 min, AUC0-t 23374 ± 4045 min ng/mL and t1/2 1065 ± 246 min.
- MeSH
- Alzheimerova nemoc MeSH
- cholinesterasové inhibitory krev MeSH
- indany krev chemie farmakokinetika MeSH
- krysa rodu rattus MeSH
- lineární modely MeSH
- piperidiny krev chemie farmakokinetika MeSH
- potkani Wistar MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- takrin analogy a deriváty krev chemie farmakokinetika MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A simple, fast and sensitive HPLC method employing dual-channel coulometric detection for the determination of repaglinide in human plasma is presented. The assay involved extraction of repaglinide by ethyl acetate and isocratic reversed-phase liquid chromatography with dual-channel coulometric detection. The mobile phase composition was 50mM disodium hydrogen phosphate/acetonitrile (60:40, v/v), pH of the mobile phase 7.5 set up with phosphoric acid. For all analyses, the first cell working potential was +380mV, the second was +750mV (vs. Pd/H(2)). Calibration curve was linear over the concentration range of 5-500nmolL(-1). Rosiglitazone was used as an internal standard. The limit of detection (LOD) was established at 2.8nmolL(-1), and the lower limit of quantification (LLOQ) at 8.5nmolL(-1). The developed method was applied to human plasma samples spiked with repaglinide at therapeutical concentrations. It was confirmed that the method is suitable for pharmacokinetic studies or therapeutic monitoring.
- MeSH
- elektrochemické techniky metody MeSH
- hypoglykemika krev chemie MeSH
- karbamáty krev chemie MeSH
- kolorimetrie metody MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- lineární modely MeSH
- piperidiny krev chemie MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- thiazolidindiony analýza MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- adukty DNA krev MeSH
- anestetika lokální krev metabolismus MeSH
- biosenzitivní techniky MeSH
- fenylkarbamáty krev metabolismus MeSH
- financování organizované MeSH
- karboxylesterhydrolasy metabolismus MeSH
- kinetika MeSH
- králíci MeSH
- lidé MeSH
- piperidiny krev metabolismus MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- zvířata MeSH
Rozpravy české akademie císaře Františka Josefa pro vědy, slovesnost a umění v Praze ; roč. VII., tř. II., č. 10.
17 s., [5] l. příl. : tab. ; 25 cm
- MeSH
- experimenty na zvířatech MeSH
- krevní oběh fyziologie MeSH
- piperidiny krev MeSH
- psi MeSH
- tkáňové extrakty fyziologie MeSH
- Check Tag
- psi MeSH
- Konspekt
- Experimentální medicína
- NLK Obory
- experimentální medicína
- angiologie
- patologie
- NLK Publikační typ
- studie
