ABSTRACT
Objective: To explore the intestinal absorption characteristics of tanshinone components self emulsifying drug delivery system (SEDDS). Methods: In situ single-pass perfusion method was used to investigate the absorption characteristics of cryptonshinone, tanshinone I, and tanshinone IIA in rats. The absorption parameters (Ka, Papp) of cryptotanshinone, tanshinone I, and tanshinone IIA were used as indicators to study their optimum absorption site among duodenum, jejunum, ileum, and colon. The effects of verapamil hydrochloride (P-glycoprotein inhibitor, P-gp inhibitor), probenecid (multi-drug resistant protein MRP2), and 2, 4-dinitrophenol (energy inhibitor) on the absorption of cryptonshinone, tanshinone I, and tanshinone IIA were also studied, as well as the effects of their different concentration. Results: Cryptonshinone, tanshinone I, and tanshinone IIA could be absorbed at all four intestinal segments, and the optimum absorption site was the upper segment of small intestine. The absorption of cryptotanshinone and tanshinone I were concentration-dependent at experimental concentration levels (1.05-4.19 mg/L and 1.22-5.56 mg/L), while tanshinone IIA was not affected obviously by its concentrations (2.43-11.12 mg/L). Verapamil hydrochloride had no significant influence on the absorption of cryptotanshinone or tanshinone I, while the absorption of tanshinone IIA was improved remarkably. Probenecid increased the absorption of cryptonshinone and tanshinone I apparently, while had no obvious effect on that of tanshinone IIA. 2,4-Dinitrophenol could decrease the absorption of cryptonshinone, tanshinone I, and tanshinone IIA apparently. Conclusion: Cryptonshinone and tanshinone I are supposed to be the substrate of MRP2 instead of P-gp. Tanshinone IIA is supposed to be the substrate of P-gp, instead of MRP2. The energy participated in the absorption of cryptonshinone, tanshinone I, and tanshinone IIA. Active absorption maybe also involved in the absorption of cryptonshinone, tanshinone I, and tanshinone IIA.