Abstract: Objective Dehydroandrographolide (DP) from Andrographis paniculata (Burm. F.) Nees is a potential anticancer
agent. This study aimed to investigate the oral bioavailability and intestinal disposition of DP to provide useful information for
the development of DP as a new candidate anticancer drug. Methods The pharmacokinetics of DP was evaluated in rats, and
its intestinal disposition was determined using cultured Caco-2 cells and a single-pass rat intestinal perfusion model. Results
The oral bioavailability of DP was 11.92% in rats. The apparent permeability coefficient (Papp) of DP from the basolateral side
(B) to the apical side (A) (5.37×10-5 cm/s) of the Caco-2 model was roughly equal to that from A to B (4.56×10-5 cm/s), suggesting
no involvement of the efflux transporter(s). In the perfusion model, no significant difference was found in the effective
permeability (P*eff) of DP between the 4 segments of the intestine. No significant metabolism of DP was detected in the
intestinal perfusates. The amount of DP found in the bile was only about 0.1% of the absorbed amount. The P*eff and bile
amounts of DP were not significantly increased by P-glycoprotein (P-gp) inhibitor or breast caner resistant protein (BCRP)
inhibitor (P>0.05). Conclusion The bioavailability of DP was 11.92% in rats. DP has good absorption and metabolism stability
in the intestine. The efflux transporters such as P-gp and BCRP do not participate in DP transport.