Journal
ACTA PHARMACOLOGICA SINICA
Volume 27, Issue 12, Pages 1642-1646Publisher
ACTA PHARMACOLOGICA SINICA
DOI: 10.1111/j.1745-7254.2006.00440.x
Keywords
oridonin; pharmacokinetics; intravenous; oral bioavailability; intraperitoneal injections; rats
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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 spec-trometric 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.
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