Pharmacelsus performed pharmacokinetic studies for several compounds in a customer´s project. Two lead compounds resulted in good bioavailability and thus the customer requested us to perform in vivo proof of concept studies on antifibrotic effects.
Following intensive literature research (free of charge for the client), Pharmacelsus set up a robust in vivo model in rats for liver fibrosis.
Fibrosis was induced either by bile duct ligation or by administration of thioacetamide. A pilot experiment was performed with a known antifibrotic drug applied at different doses.
Pharmacelsus succeeded in setting up a liver fibrosis model in the rat. General readouts are liver weight, clinical chemistry parameters (ALT, AST, T-BIL, LDL, cholesterol etc.) in plasma as well as metabolic profile in plasma and tissue. Specific readouts are available as well: Accumulation of collagen (hydroxyproline content) in liver tissue samples.
Thus the customer could stay with his trusted CRO up to proof of concept in vivo.