Comparative Analysis of the Pharmacokinetic Characteristics of 2,6-Diisobornyl-4-Methylphenol and Its Metabolites in Rat Bile under Normal Conditions and in Liver Pathology.

We studied the pharmacokinetic characteristics of phenolic antioxidant 2,6-diisobornyl-4-methylphenol (IBP) and its metabolites in rat bile following intragastric administration at a dose of 10 mg/kg to rats with toxic liver injury induced by carbon tetrachloride and healthy animals. Bile samples from each animal were collected repeatedly to study the pharmacokinetics of IBP and its metabolites. The content of the analytes was assessed by HPLC-MS/MS. In rats with liver pathology, significant changes in the pharmacokinetic parameters of IBP (a significant decrease in Cmax and AUC1-12 and an increase in MRT and T1/2) were observed along with activation of its metabolism (increased content of metabolites) in comparison with healthy animals. The results confirm the significant influence of liver pathology on the kinetics and metabolism of IBP and underscore the relevance of assessing the biliary excretion of substances at the stage of preclinical research.