Abstract: AIM: To evaluate whether Schisandrin A (SchA) can modify the pharmacokinetic profiles CYP3A substrates-midazolam in male rats. METHODS: The rats were intragastric administrated with varied dose SchA or 75 mg/kg ketoconazole for 3 consecutive days.Using of single-pass duodenum perfusion and inguinal artery -canulated rats (in vivo), midazolam metabolism was studied under chemical inhibition of CYP3A (ketoconazole) as positive control. Plasma concentrations of midazolam and related metabolites were analyzed by high performance liquid chromatography (HPLC). RESULTS: The pharmacokinetic parameters of midazolam after coadministration with SchA were as follows: AUC_(0-t) (mg·L^-1·h): (1.08±0.29) (negative control) and (1.58±0.58)(SchA 8 mg/kg) and (2.02±1.29) (SchA 16 mg/kg) and (2.22±1.25) (SchA 32 mg/kg) and 3.34±2.25 (ketoconazole 75 mg/kg);C_max (mg/L): (1.6±0.6) (negative control) and (1.8±0.8) (SchA 8 mg/kg) and (2.2±1.2) (SchA 16 mg/kg) and (2.2±0.7)(SchA 32 mg/kg) and (2.9±1.1) (ketoconazole 75 mg/kg).The pharmacokinetic parameters of 1′-hydroxy midazolam after coadministration with SchA were as follows: AUC_(0-t) (mg·L^-1·h): (0.61±0.17) (negative control) and (0.40±0.15) (SchA 8 mg/kg) and (0.39±0.20) (SchA 16 mg/kg) and (0.40±0.14) (SchA 32 mg/kg) and (0.35±0.09) (ketoconazole 75 mg/kg); C_max (mg/L): (0.54±0.13) (negative control) and (0.42±0.15)(SchA 8 mg/kg) and (0.39±0.20) (SchA 16 mg/kg) and (0.36±0.16) (SchA 32 mg/kg) and (0.35±0.12) (ketoconazole 75 mg/kg). CONCLUSION: The current results provide direct and explicit evidence that the metabolism of midazolam (a CYP3A substrate) is controlled by SchA in comparison with vehicle-treated rats.

Key words: Schisandrin A, Midazolam, 1'-hydroxy midazolam, Pharmacokinetics, CYP3A, HPLC method