Influences of Re Du Ning Injection, a traditional Chinese medicine injection, on the CYP450 activities in rats using a cocktail method

Ethnopharmacological relevance Re Du Ning Injection (RDN), a traditional Chinese medicine injection, is made from the extracts of Lonicerae japonicae flos (LJF), Artemisiae annuae herba (AAH) and Gardeniae fructus (GF). Since last decade, RDN has been widely used in China for the treatment of fever, inflammation, allergy and viral infection. Aim of the study To elucidate the potential influences of RDN on the activities of four cytochrome P450 (CYP) isozymes in rats (CYP1A2, CYP2C11 , CYP2D1 and CYP3A1/2) by “cocktail method”. Materials and methods A sensitive and specific LC–MS method capable of simultaneous quantification of four substrates and their metabolites in rat plasma was developed and validated. Relative activity estimation of four isozymes was carried out by comparing plasma pharmacokinetics of substrates and their metabolites (phenacetin/ paracetamol for CYP1A2 , tolbutamide/4-hydroxytolbutamide for CYP2C11, dextromethorphan/ dextrorphan for CYP2D1 and dapsone/N-acetyl dapsone for CYP3A1/2) between control and RDN treatment groups. Results Compared with control group, RDN at different levels could increase the total amount of tolbutamide , dextromethorphan and dapsone absorbed into blood, while decrease the total amount of phenacetin absorbed into blood at low and medium dosage and increase it at high dosage. Conclusions RDN could inhibit the activities of CYP2C11, CYP2D1 and CYP3A1/2, induce the activity of CYP1A2 at low and medium dosage but inhibit it at high dosage. The results indicated that drug co-administrated with RDN may need dose adjustment.