The Study on Biotransformation of Paeonol and Interrelation with Cytochrome P450 Enzymes

Objective: Metabolic enzymes and biotransformation of paeonol were studied by extraorgan incubation method in homogenized liver, and rational clinical administration method of paeonol was provided with scientific evidences. Methods: The content of surplus paeonol in the homogenized liver incubation solution was detected by HPLQ, and the effects of inductors and inhibitors in metabolism of paeonol were analyzed, besides metabolites and metabolic pathways of paeonol were investigated by HPLC/MS/MS . Results: The metabolic rate of paeonol in Dexamethasone (DEX) group which is the main CYP3A inductor, was significantly higher than it of the control group , however, the Phenobarbital (PB) group which is the main CYP2B inductor, had no significant difference in the metabolic rate of paeonol with control group ,moreover, Meletin, the specific CYP3A inhibitor, could significantly inhibit the metabolism of paeonol; the metabolites of paeonol in rat homogenized liver were 4-methoxyacetophenone-2-O-glucuronide and 2,4-dihydroxyacetophenone-5-O-sulphate. Conclusion: CYP3A is the main enzyme taking part in the biotransformation of paeonol in rats, and the paenol administrating simultaneously with the medicines, which have inducing and inhibiting effects on CYP3A, may probably have interactions.