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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A Liquid chromatography and tandem mass spectrometry (LC/MS/MS) method has been described for the simultaneous determination of ipriflavone and its main metabolites, 7-hydroxy-3-phenyl-chromen-4-one (M1) and 7-(4-oxo-3-phenyl-4H-chromen-7-yloxy)-propionic acid (M5) in human plasma using protein precipitation. Ipriflavone, M1, M5, and the internal standard [2-(3,4-dimethoxyphenyl)-5,7-dihydroxy-chromen-4-one] were analyzed on XTerra C 18 column with the mixture of acetonitrile-ammonium formate (10 mM, pH 3.0) (53 : 47, v/v) as mobile phase. The analytes were determined using electrospray positive ionization mass spectrometry in the multiple reaction monitoring mode. The standard curves for ipriflavone, M1, and M5 were linear over the concentration range of