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Tytuł: Estimatation the pharmacokinetic of propentofylline in organisms of rats
Abstrakt:
The purpose of this work is to estimate pharmacokinetic of propentofylline (PPF) and enantiomers of its metabolite in rats, particularly in brain which is the place of its action. First step to achieve the aim established at the beginning was to develop and validate a method of analysis of total concentration and free fraction, simultaneously PPF and enantiomers of M1 in biological matrix, according to GLP procedures. Research were conducted with using LC/MS/MS techique . Second step was the analysis of concentration of PPF and its chiral metabolite in rat’s serum and selected tissues, after single intravenous (5mg, 10 mg, 25 mg/kg) or oral application (25mg, 50 mg/kg) of PPF with taking under consideration enantioselective character of pharmacokinetic processes. The ultrafiltration and microdialysis has been used to examine free drugs fraction in serum and cortex of rats. In researches, the linearity of PPF and two-compartmental disposition has been evaluated. Furthermore, a big volume of distribution, significant klirens, and intensive hepatic and extrahepatic metabolism (for example in erytrocytes, lungs) of PPF has been shown. Distribution of PPF and M1 is significant, irregular and has nonrestrictive character. Lysosomotropism can explain mechanism of this process. The disposition M1 is stereoselective, the major enantiomer in each of examined tissues is S(+)OH PPF. It has ; been proved also, that the protein binding of examined drug has been average and this process is not enantioselective. Futhermore, the uptake by intracellular structures of examined drugs in cortex has been shown.The free fraction of examined drugs in serum recflects only to certain degree this one in cortex. The satisfactory corellation between theese concentrations has been shown for S(+)OH PPF.
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Data ostatniej modyfikacji:
10 mar 2023
Data dodania obiektu:
21 lis 2012
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http://dl.cm-uj.krakow.pl:8080/publication/749
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| Nazwa wydania | Data |
|---|---|
| ZB-111522 | 10 mar 2023 |
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