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 (P(app)) 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 cancer 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.
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 (P(app)) 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 cancer 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.