Influence of curcumin on the pharmacokinetics of lovastatin in rats with fatty liver disease

Non-alcoholic fatty liver disease is always accompanied by hyperlipemia, hypercholesterolemia and hypertension requiring to multiple drugs for the treatment at the same time, which is quite possible to incur drug/drug interactions. This study aimed at investigating the pharmacokinetics of lovastatin, which is used for lowering cholesterol in those with hypercholesterolemia and hyperlipemia, in fatty liver disease rats treated with or without curcumin, a hepatoprotective agent. Serum biochemical analysis and histopathological study were undertaken to verify that a proper non-alcoholic fatty liver rat model was established for our pharmacokinetic study and the plasma concentration of lovastatin was determined in normal rats, high fat diet fed rats treated with or without curcumin. High fat diet causing rats fatty liver disease resulted in a nearly 1. 53-fold enhancement of plasma exposure of lovastatin, as well as 2. 54-fold of t_1/2 of model group than the normal group. Curcumin treatment reversed the plasma exposure almost to the control level, as well as the level of c_max and t_1/2. The main reason might be that hepatic CYP3A2 expression decreased in high fat diet fed rats while curcumin treatment largely enhanced CYP3A2 expression. This study suggested that long-term treatment with hepatoprotective agent curcumin would influence the pharmacokinetic behaviour of other drugs and the drug/drug interaction between hepatoprotective agents and co-prescribed drugs should be of concern during liver injury.