Home
Resources
Publications
Preclinical Pharmacokinetics of SB-203580, a Potent Inhibitor of p38 Mitogen-Activated Protein Kinase

Preclinical Pharmacokinetics of SB-203580, a Potent Inhibitor of p38 Mitogen-Activated Protein Kinase

K W Ward, J W Prokscht, L M Azzaranot, J A Mumawa, T J Roethke, G J Stelman, M J Walsh, K S Zeigler, J E McSurdy-Freed, J R Kehlert, J Chokshi, M A Levy, B R Smith

Xenobiotica. 2001 Nov;31(11):783-97.

PMID: 11765141

Abstract:

1. SB-203580 (4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl)imidazole) is a potent, selective inhibitor of p38 MAP kinase used extensively as a tool inhibitor in various pharmacological and toxicological models. This study was designed to evaluate the pharmacokinetics of SB-203580 in several preclinical species, both to assist with the interpretation of existing studies and to aid in the design of future studies with this inhibitor. 2. In vitro, SB-203580 was stable in mouse, rat, dog, monkey and human plasma over 24 h. However, species differences in plasma protein binding were observed; SB-203580 was 96-97% bound in human plasma and 78-92% bound in other species. These data suggest that protein binding may influence the results of in vitro studies using SB-203580, particularly when comparing results from different in vitro systems that incorporate plasma components. In vivo, SB-203580) demonstrated moderate to high clearance in all species tested, with non-linear elimination observed in the rat at plasma concentrations > 1,000 ngml(-1). Although good solution bioavailability was observed in non-rodents (78% in dog, 32% in monkey), lower and more variable bioavailability was observed in the rat and mouse (3 -48%). 3. These interspecies differences in bioavailability, and the non-linear pharmacokinetics observed in rat, highlight the importance of monitoring SB-203580 systemic exposure in parallel witb the pharmacological endpoint during in vivo pharmacology

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP152121476-A	SB 203580		152121-47-6	Price
IAR42415514	InSolution SB 203580			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: