The study was conducted to assess the functional status of CYP3A4 substrate (atorvastatin) in hepatotoxicity model treated with silymarin and rutin for a period of 14 days in rats. Hepatotoxicity was induced with acetaminophen (500 mg/Kg po once daily for 3 days) in adult male Wistar rats in 3 groups. Group 1: Normal control, Group 2, 3 and 4 were administered distilled water

(5 ml/kg po once daily), silymarin (25 mg/Kg po once daily) and rutin (20 mg/Kg po once daily), respectively subsequently for 11 days from the last dose of acetaminophen. On the 15th day, a CYP3A4 substrate (atorvastatin @ 10 mg/kg po) was administered in all the groups and blood samples were collected at predetermined intervals. Pharmacokinetic interaction studies

were conducted for evaluation of CYP3A4 activity using the specific substrate atorvastatin in all the groups. Mean plasma concentration (Cmax), half-life (t1/2β), area under the plasma cconcentration-timecurve (AUC) and mean residence time (MRT) of groups 2 and 4 were signifi cantly (p<0.05) increased and elimination rate constant (β) was signifi cantly (p<0.05) decreased in acetaminophen treated group as comparison to the normal control group. The kinetic profile of silymarin-treated group 3 was comparable to group 1 for single dose study. All the pharmacokinetic parameters of atorvastatin revealed significant correlations between hepatotoxic control and rutin treated group, while silymarin treated group showed signifi cant alterations in the kinetic profile suggesting its hepatoprotective effect.