Pharmacokinetics And Distribution Study Of Oridonin

Background and object: Oridonin is one of the effective ingredients extracted from Rabdosin Rubdesens Hemsl, which is used widely in clinic. Its main effects are relieving superficies by cooling, anti-inflammatory, odynolysis, invigorating stomach, promoting blood flow, anti-tumor etc. Mainly used for sore throat, tonsillitis, flu, headache, bronchitis, chronic hepatitis, rheumatoid joint pain, Snake bites. In recent years, because of the significant anti-tumor effect, related pharmacological studies of ORI are more extensive and intensive. This article has reported pharmacokinetics of ORI in mice and rabbit, distribution of ORI in mouse tissues. The object of this study was to reveal the absorption and metabolism of ORI in experimental animal, to provide guidance for its pharmacological and toxicological study and clinical practice.Methods: (1) Pharmacokinetics of ORI in mice: mice were i.v. administrated ORI with dosage of 10 mg·kg^-1, plasma sample was obtained before administration and when 1, 5, 15, 30, 60, 90, 120, 180, 240 min after administration, then set up HPLC method for detection plasma drug concentration of ORI in mice and to invest the pharmacokinetics; (2) Distribution of ORI in mice: mice were i.v. administrated ORI with dosage of 10 mg·kg^-1, the tissues of heart, liver, spleen, lung, kidney and brain were obtained when 0.083(5 min), 0.25, 0.5, 1, 2, 4, 6, 12 h after administration. The concentrations of ORI in tissues were detected by HPLC. (3) Pharmacokinetics of ORI in rabbit: rabbit was i.v. administrated ORI with dosage of 3.7 mg·kg^-1, plasma sample was obtained before administration and when 0.25, 0.5, 1, 2, 4, 6, 8, 12 h after administration. The plasma concentration of ORI was detected by HPLC, the data was processed with the 3P97 software, to research the pharmacokinetic characteristics of ORI in rabbits.Result: (1) The major pharmacokinetic parameters of ORI single dose in mice: T_1/2α=1.2499 min, T_1/2β=42.6384 min, K₂₁=0.1523 min^-1, K₁₂=0.3593 min^-1, K₁₀=0.0592 min^-1, AUC=366.0350μg·min·mL^-1, CL=0.0273 L·min^-1·kg^-1, V_C=0.4615 L·kg^-1. (2) The distribution of ORI in mice: after i.v. ORI, at the time of 0.083 h all tissues had a higher concentration. Heart was the highest. Kidney and liver were second, and then followed by lung, spleen and brain. Liver and kidney were detected had the highest concentration of its organization in 0.25 h, and the concentration of ORI decreased with time as the same as other organizations. Brain detected low concentration of ORI. (3) The major pharmacokinetic parameters of ORI single dose in rabbit: T_1/2α=0.100 h, T_1/2β=1.725 h, K₂₁=1.612 h^-1, K₁₂=3.979 h^-1, K₁₀=1.723 h^-1, AUC=56.516μg·h·mL^-1, CL=0.065 L·h^-1·kg^-1, V_c = 0.038 L·kg^-1.Conclusion: The HPLC method of our experiment is sensitiveness, fast and stable; after i.v. administration, oridonin was distributed as two-compartment model in mice and rabbit, metabolism of ORI was very soon and T1/2 is short; oridonin was distributed highest in mouse heart, kidney and liver, lower in spleen and lung, an lowest in brain.