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Świerczek, Artur
2020
Praca doktorska
In this work, the selectivity of lisofylline ((±)-LSF) and GRMS-55 as phosphodiesterase (PDE) inhibitors and their anti-inflammatory activity in in vitro tests were assessed. Pharmacokinetics of both compounds in rats and the influence of experimentally induced inflammatory diseases on pharmacokinetics of (±)-LSF were evaluated. Moreover, the efficacy of these compounds in animal models of autoimmune hepatitis (AIH), endotoxemia (ET), and rheumatoid arthritis (RA) was evaluated. The usefulness of cAMP as a marker of pharmacological response was tested. The data collected were analyzed using pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) modeling. The studied compounds exhibit a favorable PDE inhibitory profile. Cyclic AMP is a useful marker of pharmacological response following administration of PDE4 inhibitors. The results of simulations indicate that a continuous intravenous infusion is an optimal dosing schedule of LSF in clinical trials. (±)-LSF and GRMS-55 decreased level of TNF-α in plasma of rats with ET and inhibited the progression of RA. GRMS-55 displayed efficacy in AIH. The studied compounds, due to their favorable PK and PD properties, are promising candidates for further preclinical and clinical studies. The developed mathematical models may be used in future studies on new compounds with immunomodulatory and anti-inflammatory activities.
Kraków
2 - studia doktoranckie
biochemia ; farmakologia
Wydział Farmaceutyczny
Wyska, Elżbieta
oai:dl.cm-uj.krakow.pl:4456
ZB-132515
pol; eng
tylko w bibliotece
Jan 26, 2022
2
http://dl.cm-uj.krakow.pl:8080/publication/4457
RDF
OAI-PMH
Istrati, Julita
Wróbel, Aldona
Klimek, Ewa
Staszkiewicz, Magdalena
Włoch, Alicja
Wróbel, Piotr
Citation style: chicago-author-date iso690-author-date
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