Pharmacokinetic study of paeonimetabolin I, a major metabolite of paeoniflorin from paeony roots.

Plasma concentrations of paeoniflorin (PF) and its major metabolite, paeonimetabolin I (PM-I), were estimated after oral administration of PF to rats at doses of 0.5 and 5 mg/kg. The maximal plasma concentrations (Cmax) of PF were 9.9 and 20.3, and those of PM-I were 16.5 and 101.7 ng/ml at each dose, respectively. The times to Cmax (tmax) of PF were 11.6 and 13.3, and those of PM-I were 60 and 80 min, respectively. The AUC(0-180) of PM-I were 1873 and 12358, and those of PF were 300 and 1174 ng min/ml, respectively. On the other hand, after intravenous administration of PM-I to rats at doses of 0.2 and 2 mg/kg (equal in molar ratio to 0.5 and 5 mg/kg PF), the plasma concentration of PM-I decreased rapidly and the plasma concentration-time curve profile of it fitted well with the two-compartment model at each dose, with terminal half lives (t1/2) of 90.9 and 90.6 min. The Vdss values were 0.91 and 3.79 l/kg, the CLtot values were 8.7 and 39.9 ml/min kg, and the AUC(0-180) values were 5614.1 and 13176.0 ng min/ml, at each dose, respectively. The significant increase in Vdss and CLtot with increasing doses suggested dose-dependent pharmacokinetics. When PM-I was given orally at the same doses, the following parameters were shown: Cmax of 102.2 and 285 ng/ml at tmax 6.2 and 7.5 min and AUCs of 4145.6 and 14182.1 ng min/ml, at each dose. The bioavailability (F) values were 0.8 and 1.07, respectively. These findings indicated that the high percentage of PM-I transformed by intestinal bacteria was rapidly absorbed from the gastrointestinal tract, and a significantly high concentration of PM-I, rather than PF, was present in the plasma after oral administration of PF.