Pharmacokinetic behaviors and oral bioavailability of oridonin in rat plasma.
OBJECTIVE
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%.


CONCLUSIONS
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.
Xu
Wen
W
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Sun
Jin
J
Zhang
Ting-ting
TT
Ma
Bo
B
Cui
Sheng-miao
SM
Chen
Da-wei
DW
He
Zhong-gui
ZG
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004224:Diterpenes / Q000008:administration & dosage* / Q000302:isolation & purification / Q000493:pharmacokinetics*; D045786:Diterpenes, Kaurane / Q000008:administration & dosage* / Q000302:isolation & purification / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D037602:Isodon / Q000737:chemistry; D008297:Male; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D004224:Diterpenes; D045786:Diterpenes, Kaurane; C011959:oridonin