The pharmacokinetics of oleanolic acid was evaluated in vitro and in vivo. From Caco-2 cell permeation studies, oleanolic acid was a low permeability compound with no directional effects, suggesting a low in vivo absorption mediated by a passive diffusion. Oleanolic acid was metabolically unstable following incubation with rat liver microsomes in the presence of NADPH. After intravenous injection at doses of 0.5, 1 and 2 mg/kg doses, oleanolic acid showed dose-linear pharmacokinetics as evidenced by unaltered CL (28.6-33.0 ml/min/kg), Vss (437-583 ml/kg), dose-normalized AUC (16.0-17.9 microg min/ml based on 1 mg/kg) and t1/2 (41.9-52.7 min). Following oral administration of oleanolic acid at doses of 10, 25 and 50 mg/kg, Tmax, t1/2, dose-normalized Cmax (66-74 ng/ml based on 25 mg/kg) and dose-normalized AUC (5.4-5.9 microg min/ml based on 25 mg/kg) were comparable between 25 and 50 mg/kg dose, but the plasma concentrations at 10 mg/kg dose were not measurable as they were below the limit of quantitation (2 ng/ml). The absolute oral bioavailability was 0.7% for oral doses of 25 and 50 mg/kg. The extent of urinary excretion was minimal for both i.v. and oral doses. The very low oral bioavailability of oleanolic acid could be due to a poor absorption and extensive metabolic clearance.

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The pharmacokinetics of active components such as baicalein, wogonin and oroxylin A were evaluated after oral administration of a purified extract of Scutellaria baicalensis GEORGI (PF-2405) containing the high contents of baicalein, wogonin and oroxylin A to rats. Following oral administration of PF-2405 at 10, 20 and 40 mg/kg dose (equivalent to 4.5, 9.0 and 18 mg/kg baicalein), a major constituent baicalein and its active metabolite baicalin showed dose-linear pharmacokinetics as evidenced by unaltered dose-normalized AUC, dose-normalized Cmax, Ae(0-30h) and GI(30h) values. Following oral administration of PF-2405 at three doses (equivalent to 0.4, 0.8 and 1.6 mg/kg wogonin), dose-normalized Cmax and dose-normalized AUC were comparable between the 20 and 40 mg/kg PF2405 doses, but plasma concentrations of wogonin at 10 mg/kg of PF-2405 were not measurable as they were below limit of quantitation (LOQ; 18 pmol/mL). Following oral administration of PF-2405 at the three doses (equivalent to 1.5, 3.0 and 6.0 mg/kg oroxylin A), the concentrations of oroxylin A in plasma, urine and gastrointestine samples were below the assay LOQ (18 pmol/mL). Significant differences in AUCs, Ae(0-30h) and GI(30h) values for baicalein and baicalin were observed after oral administration of pure baicalein (18 mg/kg) and PF-2405 (40 mg/kg). The increases in AUCs of baicalein and baicalin after oral administration of PF-2405 may have been due to the significant decrease in GO(30h) values for baicalein.