Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study

BACKGROUND AND OBJECTIVE: Dan-Hong injection, which comprises extracts of Salvia miltiorrhiza and Carthamus tinctorius, promotes blood circulation and reduces blood stasis. Combination of S. miltiorrhiza and C. tinctorius is more effective in treating cerebral ischemia than S. miltiorrhiza alone. This study aimed to examine the pharmacokinetic characteristics of four active ingredients of S. miltiorrhiza and C. tinctorius, namely danshensu (DSS), hydroxysafflor yellow A (HSYA), and salvianolic acid A (SAA) and B (SAB) in normal and cerebral ischemia rats. METHODS: Normal and cerebral ischemia rats were injected via the tail vein with each active ingredient, and blood was collected through the jaw vein at different time points. The plasma concentration of the compatibility group was analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using Pharmacokinetic Kinetica 4.4 software. RESULTS: The pharmacokinetics of the four active ingredients in the normal and cerebral ischemia rats were consistent with a two-compartment model. The area under the concentration–time curve was higher in normal rats than in cerebral ischemia rats, with a highly significant difference for SAA (P < 0.01). Clearance rates were lower in normal rats than in cerebral ischemia rats, with DSS showing the most significant difference (P < 0.01). Furthermore, there were significant differences between normal and cerebral ischemia rats in the distribution phase-elimination half life for DSS, SAA, and HSYA, as well as in the apparent volume of distribution for the central compartment for DSS and HSYA (P < 0.01). The plasma concentrations of the four active ingredients were higher in normal rats than in cerebral ischemia rats. CONCLUSION: Cerebral ischemia rats showed higher drug clearance rates and longer retention times than normal rats, which may be due to destruction of the blood–brain barrier during cerebral ischemia–reperfusion. The four active ingredients likely integrated and interacted with each other to affect target sites in the brain to protect against cerebral ischemic injury.