Pharmacokinetic study of 4-methylumbelliferone in mice.
The pharmacokinetic behavior of 4-methylumbelliferone (4-MU), a compound known to be excreted as conjugated metabolites, was studied in mice and the results were compared with those reported in rats. Plasma half-life of the terminal phase (t1/2,beta) of mice after an intravenous administration of 4-MU was approximately one-twenty fifth of that of rats. Mice showed a dose dependency in both hepatic and extrahepatic clearances, though dose dependent hepatic clearance is reported to be the main route of elimination in rats. In the same dose range (10-25 mg/kg), the hepatic intrinsic clearance per unit body weight of mice was approximately 5 times larger than that of rats. The blood-to-plasma concentration ratio and the unbound volume of distribution of tissues of mice were smaller than those of rats. It was concluded that the shorter t1/2,beta of mice than that of rats may be due to the larger hepatic clearance, the presence of extrahepatic clearance and the smaller volume of distribution.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D005965:Glucuronates / Q000378:metabolism; D006923:Hymecromone / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011485:Protein Binding; D051381:Rats; D013045:Species Specificity; D013431:Sulfates / Q000378:metabolism; D014018:Tissue Distribution; D014468:Umbelliferones / Q000378:metabolism*
D001798:Blood Proteins; D005965:Glucuronates; D013431:Sulfates; D014468:Umbelliferones; D006923:Hymecromone