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• W2158943197 abstract "Novel 5-benzilidene thiazolidinones have been synthesized and exhibited anti-inflammatory activity. In this work one of the compounds of the thiazolidinone chemical series, (5Z,E)-3-[2-(4-chlorophenyl)-2-oxoethyl]-5-(1H-indol-3-ylmethylene)-thiazolidine-2,4-dione (PG15) was investigated aiming to determine the drug's anti-inflammatory potential in pre-clinical studies.Methods used included the in-vitro inhibition of cyclooxygenase-1 and -2, in-vivo evaluation of anti-inflammatory activity by air pouch and peritonitis models and the pharmacokinetic profile after intravenous (3 mg/kg) and oral (3 and 6 mg/kg) dosing to rats.A two-compartment model with a fast distribution and an elimination half-life of 5.9 +/- 3.8 h described the PG15 plasma profile after intravenous dosing. PG15 showed an erratic and rapid absorption following oral administration with peak concentrations between 0.5 and 1 h. PG15 0.1 microM inhibited more than 30% and 13% of purified cyclooxygenase-1 and -2 activity in vitro, respectively. A lack of dose dependency was observed for the anti-inflammatory effect in the dose range investigated (0.8-50 mg/kg), with a maximum of 67.2 +/- 4.6% inhibition of leucocyte migration in the carrageenan-induced air pouch model obtained with the 3 mg/kg dose, similar to that observed for indometacin 10 mg/kg.The erratic absorption of PG15 observed after oral dosing could explain the lack of anti-inflammatory dose dependency." @default.
• W2158943197 created "2016-06-24" @default.
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• W2158943197 date "2009-03-01" @default.
• W2158943197 modified "2023-09-25" @default.
• W2158943197 title "Preclinical pharmacokinetic and pharmacodynamic evaluation of thiazolidinone PG15: an anti-inflammatory candidate" @default.
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• W2158943197 doi "https://doi.org/10.1211/jpp/61.03.0008" @default.
• W2158943197 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19222906" @default.
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