Comparative pharmacokinetic study of theaflavin in healthy and experimentally induced liver damage rabbits

Abstract

This current work aimed to study the pharmacokinetics of theaflavin in healthy and hepatotoxic rabbits for comparison. Aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were significantly raised (P<0.05) after administration of 0.2 mg/kg body weight (BW) Carbone tetrachloride (CCL4) subcutaneously. Pharmacokinetic parameters calculated following administration of theaflavin intravenously and orally at 30 mg/kg and 500 mg/kg respectively to both healthy animals and those with damaged liver. Theaflavin concentration in blood measured by HLPC at various time intervals. Pharmacokinetic results showed that theaflavin concentration when given orally reached its maximum concentration after 5 hours in healthy rabbits. While in hepatotoxic group, theaflavin concentration achieved the highest level in blood after three hours. Theaflavin bioavailability in hepatotoxic animals was significantly high and almost double its bioavailability in healthy animals. Results revealed that the area under curve (AUC) value in rabbits with damaged liver was significantly greater than in healthy group (P<0.05). t ½ of theaflavin after intravenous administration was 6.3±0.82 hour in damaged liver group which is significantly higher than that in healthy group (P<0.05). Theaflavin mean concentration in hepatotoxic group required more than 3 hours to decline to 352±19.4 ng/ml when compared to its concentration in healthy group which is required only 45 minutes to decrease to 310± 9.5 ng/ml. In conclusion liver has critical impact on the pharmacokinetics of theaflavin especially bioavailability and biotransformation and this research recorded reasonably large differences between healthy and liver damaged groups regarding theaflavin pharmacokinetic parameters which may result in negative influences on its biological efficacy when used in the treatment of various diseases.

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