Abstract

Aim:Oridonin is a new anti-tumor drug candidate with promising antitumor activity. The aim of the present study is to investigate the single- and repeated-dose pharmacokinetics of injectable beta-cyclodextrin-oridonin inclusion complex in rats. Methods: Rats were given single- or multiple-dose (7 days) of injectable beta-cyclodextrin-oridonin inclusion complex (single-dose: 33 mg/m2, 99 mg/m2, 296 mg/m2; repeatede-dose: 99 mg/m2 calculated as oridonin) by intravenous injection. Plasma oridonin was analyzed by LC–ESI-MS. The main pharmacokinetics parameters were calculated and compared. Results: The PK data of single-dose injectable beta-cyclodextrin-oridonin inclusion complex in rats were best fit by a three-compartment model.The terminal elimination half-life (t1/2z) of oridonin ranged from 8.72±1.14 to 10.87±2.03h. AUC (0-t) and Cmax for oridonin showed statistically significant differences (p < 0.05) between singledose and repeated dose. Conclusion: Our study has led to the view that injectable beta-cyclodextrin-oridonin inclusion complex can increase the bioavailability of oridonin in rats and is suitable for once a day dosing. However, caution should be taken when injectable beta-cyclodextrin-oridonin inclusion complex is given by i.v. repeatedly.

Key words: Pharmacokinetics; Oridonin; Beta-cyclodextrin; rats