Effects of the coexisting diterpenoid tanshinones on the pharmacokinetics of cryptotanshinone and tanshinone IIA in rat

Tanshinone IIA and cryptotanshinone are the main pharmacologically active components in the Chinese herb drug Salvia miltiorrhiza Bge. The objective of this study was to investigate the effect of coexisting tanshinones in liposoluble ethanol extract of S. miltiorrhiza Bge. on the rat pharmacokinetics of tanshinone IIA and cryptotanshinone after oral intra-gavage administration of the tanshinones extract. Rats were given the tanshinones extract 23.3 mg/kg (equivalent to 5.7 mg/kg cryptotanshinone and 8.0 mg/kg tanshinone IIA), cryptotanshinone 5.7 mg/kg, or tanshinone IIA 8.0 mg/kg orally under overnight fasted conditions. Blood samples were taken at predetermined sampling time interval and the concentrations of cryptotanshinone and tanshinone IIA were determined by a validated LC–MS/MS method. The peak plasma concentrations of cryptotanshinone and tanshinone IIA were considerably increased (about 8 and 10 folds) after oral administration of the extract in comparison with the equivalent dose of single component administration, respectively. The areas under the plasma concentration–time curve (AUC) of cryptotanshinone and tanshinone IIA were both significantly increased (P < 0.001) as well. Tanshinone IIA was also found after the administration of cryptotanshinone alone, and the fraction of metabolism of tanshinone IIA was 21.0 ± 4.1%. Therefore, the pharmacokinetics of cryptotanshinone and tanshinone IIA in rats after administration of the tanshinones extract were significantly affected by the coexisting tanshinones. In conclusion, the herb-drug interactions occurred between coexisting tanshinones and cryptotanshinone or tanshinone IIA affected their absorption, transformation and metabolism.