Effect Of Compound Wurenchun Capsules On The Concentration Of Tacrolimus And The Protection Of Liver Injury

Tacrolimus (FK506) is a macrolide immunosuppressant, which is expensive and has low bioavailability in clinical applications. Meanwhile, FK506 is a long-term or even lifelong medication for patients. Tacrolimus also dose damage to liver and kidney. How to improve the bioavailability of FK506, mitigate damage to liver and kidney caused by anti-rejection drugs has become the focus of attention in clinical medicine.Wuzhi capsule is prepared from Schisandra chinensis. The main chemical composition is lignin. It is reported that Wuzhi capsule in conjunction with FK506 can improve the bioavailability of FK506, also reduce its toxicity to liver and kidney.Compound Wurenchun capsules (CWC) is a compound preparation of Schisandra chinensis, Panax notoginseng, Chinese thorowax root and Phyllanthus urinaria. Schisandra chinensis is the monarch drug in CWC. The hepatoprotective effect of CWC is superior to other similar medicine in market. The formulation also contains Schisandra Lignans. Studies have shown that the. formulation contained notoginseng saponins can also improve the bioavailability of FK506, Panax notoginseng, Chinese thorowax root and Phyllanthus urinaria have strong hepatoprotective effect, so it is presumed that CWC in combination with FK506 in liver transplant patients anti-rejection therapy, can improve the bioavailability of FK506 and mitigation of liver toxicity which is superior to Wuzhi capsule.In this paper, we studied the effect of compound Wurenchun capsules on the concentration of tacrolimus and the protection of liver injury. Two following studies were conducted in this paper:The first part is literature review which illustrated the progress in the studies of effects of Schisandra chinensis and its preparations on the plasma concentration of anti-rejection drugs and in the research of Schisandra chinensis and its preparations for prevention and treatment of drug of liver injury.The second part is the experimental study, including the following 3 aspects:Part I, The effect of single administration of compound Wurenchun capsules on on the concentration of tacrolimus.Objective Explore the effect of single administration of compound Wurenchun capsules on tacrolimus pharmacokinetics. Methods 12 SD rats were divided into the FK506 administered alone group and CWC co-administered with FK506 group Determing the concentration of FK506 in rat plasma. Compare the concentration of FK506 and the pharmacokinetic parameters of two groups. Results Cmax of FK506 in CWC combination group was 1.9 times of FK506 alone administration group, and AUCo-t was 3.4 times. Conclusion ingle dose of CWC in combination with FK506 can significantly increase the blood concentration of FK506 and improve the bioavailability of FK506.Part â…¡, The effect of pretreatment with compound Wurenchun capsules on on the concentration of tacrolimus.Objective Explore the effect of pretreatment with compound Wurenchun for 7d on pharmacokinetics of tacrolimus. Methods Six SD male rats were repeatedly administrated with CWC for one week, then were dosing with FK506. Blood concentration of FK506 is detected. The pharmacokinetic parameters were calculated. Results Compared with single dose of CWC combined with FK506 group, Cmax of FK506 in pretreatment with CWC for 7 days group increased to 3.9 times and AUCoâ†'t increased to 4.4 times. Conclusion retreatment with CWC for seven days can increase the bioavailability of FK506,and is more effective than a single dose CWC.Part â…¢, The effect of tacrolimus in combination with compound Wurenchun capsules for seven days on the concentration of tacrolimus and the protection of hepatic injury.Objective Explore the effect of tacrolimus in combination with compound Wurenchun capsules for seven days on the concentration of tacrolimus and the protection of hepatic injury. Methods 18 SD rats were divided into blank control group, the FK506 administered alone group and FK506 joint administration with CWC for 7 days group. The blood samples were taken from the abdominal aorta to detect the plasma concentration and liver function. Results The rats were sacrificed and the liver tissue was taken for pathological observation. The measurement results show that plasma concentrations of FK506 associated with CWC group showed significant difference compared with FK506 alone group (P<0.01). Liver function test results showed that FK506 alone group had abnormal liver function than control group. Alanine aminotransferase (ALT) level in FK506 was lower than blank control group (P<0.05). ALT level in FK506 associated with CWC group was lower than FK506 alone group (P<0.01). The rat liver tissue slices of FK506 alone group showed obvious inflammatory phenomena. The inflammation was eased in FK506 associated with CWC group. Conclusion CWC combined with FK506 can significantly increase the blood concentration of FK506 and effectively alleviate liver damage caused by FK506.In summary, CWC can effectively improve the blood concentration and bioavailability of FK506, alleviate liver damage caused by FK506.