To study the pharmacokinetic profile of atorvastatin in experimental hepatotoxic untreated and treated rats with N-acetyl cysteine and Costus pictus
with special reference to assess the functional status of CYP3A4.
Materials and Methods: Twenty Sprague dawley rats of 3 months age were divided into 4 groups, comprising of 5 rats in each group. Acetaminophen (APAP) @ 500 mg/kg BW was administered orally to all the groups except group 1 from day 1 to 3. Group 1 was maintained as normal control. Group 2 was subsequently administered with distilled water (p/o) from day 4 to 17 and was considered as toxic control. Groups 3 and 4 were administered (p/o) with N-Acetyl cysteine @ 300 mg/kg BW and Costus pictus aqueous extract @ 500 mg/kg BW, respectively from day 4 to 17. Atorvastatin was administered on day 18 as single oral dose in all the groups and blood samples were drawn at specified intervals for pharmacokinetic analysis.
Results: Atorvastatin metabolism was altered in APAP treated toxic group, which was reflected in increase in Cmax, AUC0-t, AUMC0-t, AUC0-∞ and AUMC0-∞ that eventually resulted in prolonged t1/2β, MRT and decrease in clearance. Among the treated groups, group 3 (N-acetyl cysteine) revealed better metabolic profile of CYP3A4 as compared to group 4 (Costus pictus extract).
Conclusion: The treated groups revealed significant alteration in the pharmacokinetic profile that supports the functional status of CYP3A4 and when groups 3 and 4 are compared, the pharmacokinetic profile was found better in group 4 in comparison to group 3 suggesting that N-acetyl cysteine is more potent than Costus pictus in the hepatoprotective activity.