Pharmacokinetic Analysis of Atorvastatin with Silymarin and Rutin in Hepatotoxic Rats with a Special Reference to Functional Status of CYP3A4 Enzyme
Reddy Mannem Kasi, Reddy Alla Gopala, Gopu Boobalan*, Reddy Muskula Anudeep, Venkat Chitturi Sree, Kumar Satish, Kumar Matham Vijay
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Science, Rajendranagar, Hyderabad, India
*Corresponding author: G Boobalan, Email: email@example.com
Online published on 7 February, 2017.
The study was conducted to assess the functional status of CYP3 A4 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 15* day, a CYP3A4 substrate (atorvastatin @ 10 mg/k gpo) 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 (Cimx), half-life (ti;, P), area under the plasma concentration time curve (AUC) and mean residence time (MRT) of groups 2 and 4 were significantly (p<0.05) increased and elimination rate constant (|3) was significantly (p<0.05) decreased in acetaminophen treated group as comparison to the normal control group. The k inetic profile of silymarin-treated group 3 was comparable to group 1 for single dose study. All the pharmacok inetic parameters of atorvastatin revealed significant correlation between hepatotoxic control and rutin treated group, while silymarin treated group showed significant alterations in the k inetic profile suggesting its hepatoprotective effect.
Acetaminophen, Atorvastatin, CYP3A4, Rutin, Silymarin.