Author: "Shimozono R" / Topic: caspase inhibitors - Searchworks@Jio Institute Digital Library Search Results

Author: Ueno Y, Ohmi T, Yamamoto M, Kato N, Moriguchi Y, Kojima M, Shimozono R, Suzuki S, Matsuura T, and Eda H
Subjects: Administration, Oral, Alanine Transaminase blood, Alanine Transaminase drug effects, Animals, Antibodies, Monoclonal toxicity, Antibodies, Monoclonal, Murine-Derived, Apoptosis drug effects, Chemical and Drug Induced Liver Injury, Disease Models, Animal, Drug Administration Schedule, Drug Delivery Systems, Enzyme Inhibitors administration & dosage, Enzyme Inhibitors pharmacokinetics, Liver metabolism, Male, Mice, Mice, Inbred BALB C, Pentanoic Acids administration & dosage, Pentanoic Acids pharmacokinetics, Tissue Distribution, Caspase Inhibitors, Enzyme Inhibitors pharmacology, Liver Diseases drug therapy, Pentanoic Acids pharmacology
Abstract: In a mouse model of alpha-Fas-induced acute liver injury, the orally-administered caspase inhibitor PF-03491390 (formerly named IDN-6556) was retained in the liver for prolonged periods with a low systemic exposure. Reductions in the elevated plasma levels of alanine aminotransferase (ALT) revealed that the retention of PF-03491390 in the liver exerted a hepatoprotective effect, even when pre-administered to mice 4 h before alpha-Fas insult. Prolonged retention of PF-03491390 in the liver after oral administration has the benefit of low systemic exposure, making this a beneficial agent for the treatment of liver diseases.
Published: 2007
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