Pharmacokinetic-pharmacodynamic studies of phosphodiesterase inhibitors – lisofylline and GRMS-55 with anti-inflammatory and immunomodulatory properties - Digital Medical Library

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Title: Pharmacokinetic-pharmacodynamic studies of phosphodiesterase inhibitors – lisofylline and GRMS-55 with anti-inflammatory and immunomodulatory properties

Author:

Świerczek, Artur

Date:

Type:

Praca doktorska

Abstract:

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.

Place of publishing:

Level of degree:

2 - studia doktoranckie

Degree discipline:

biochemia ; farmakologia

Degree grantor:

Rada Dyscypliny Nauki farmaceutyczne

Promoter:

Wyska, Elżbieta

Date issued:

Identifier:

oai:dl.cm-uj.krakow.pl:4456

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Language:

Access rights:

tylko w bibliotece

Subject and keywords:

PK/PD modeling disease progression modeling phosphodiesterase inhibitors rheumatoid arthritis autoimmune hepatitis

Object collections:

Digital Medical Library > PhD thesis database

Last modified:

Apr 15, 2024

In our library since:

Jan 26, 2022

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10

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0

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http://dl.cm-uj.krakow.pl:8080/publication/4457

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ZB-132515	Apr 15, 2024

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