Acta Pharmacologica Sinica 2006 December; 27 (12): 1642-1646; doi: 10.1111/j.1745-7254.2006.00440.x

Aim: To study the intravenous and oral pharmacokinetic behavior of oridonin and its extent of absolute oral bioavailability in rats.

Methods: Oridonin was administered to rats via iv (5, 10 and 15 mg/kg), po (20, 40 and 80 mg/kg) or ip administration (10 mg/kg). The concentrations of oridonin in rat plasma were determined by a high performance liquid chromatography with electrospray ionization mass spectrometric detection (HPLC/ESI-MS) method and the pharmacokinetic parameters were determined by non-compartmental analysis.

Results: The plasma concentration of oridonin after intravenous administration decreased polyexponentially, and the pharmacokinetic parameters of oridonin were dose-independent within the examined range. Oridonin was absorbed rapidly after oral gavage with a t_max of less than 15 min; the extent of absolute bioavailability of oridonin following oral administration was 4.32%, 4.58% and 10.8%. The extent of absolute bioavailability of oridonin following intraperitoneal administration was 12.6%.

Conclusion: First order rate pharmacokinetics were observed for oridonin within the range of iv doses, while the extent of absolute oral bioavailability was rather low and dose- dependent. The low and dose-dependent extent of oral bioavailability may be due to the saturation of first-pass effects.

Keywords: oridonin; pharmacokinetics; intravenous; oral bioavailability; intraperitoneal injec-tions; rats