【摘要】 目的 系统评价五酯胶囊对他克莫司（tacrolimus,TAC）血药浓度、药动学参数和肝肾功能的影响。方法 在国内外各大中英文数据库中，系统检索TAC联合五酯胶囊治疗肝移植受者的临床随机对照试验（randomized controlled trial,RCT）以及前瞻性自身对照研究，检索研究时限截至2023年1月。2名研究人员依据研究文献的纳入及排除标准相互独立完成研究检索、数据提取及方法学质量评价，对联合应用五酯胶囊后肝移植受者TAC的血药浓度、肝肾功能及药动学参数进行Meta分析。结果 最终纳入8篇文献，共381例肝移植受者。Meta分析结果：与不联合五酯胶囊比较，①采用TAC联合应用五酯胶囊1个月及2个月后，肝移植受者TAC血药浓度分别为[SMD=0.83,95%CI（0.34,1.31）,P=0.000 8]、[SMD=0.57,95%CI（0.17,0.97）,P=0.005]，差异有统计学意义；3个月及6个月后差异无统计学意义；②药动学参数：联用五酯胶囊后，肝移植受者体内TAC的药时曲线下面积(area under curve,AUC_0→t)[SMD=1.97,95%CI（1.27,2.66）,P<0.000 01]，达峰时间(peak time,T_max)[SMD=-0.85,95%CI（-1.45,-0.25）,P=0.005]，峰浓度(peak concentration,C_max)[SMD=1.79,95%CI（0.82,2.75）,P=0.000 3]，差异均有统计学意义；③联用TAC及五酯胶囊后，丙氨酸氨基转移酶（alanine aminotransferase,ALT）[SMD=-1.03,95%CI（-1.80,-0.25）,P=0.010]，差异有统计学意义，总胆红素（total bilirubin,TB）、血清肌酐（serum creatinine,Cr）差异无统计学意义。结论肝移植受者在接受以TAC为基础的相关免疫抑制方案的同时，联合使用五酯胶囊，可在用药早期使TAC达到更高血药浓度，且长期用药不影响TAC在肝移植受者体内稳态浓度。此外，联用五酯胶囊可一定程度改善肝移植受者肝功能且不影响肾功能与胆汁排泄。药动学方面，五酯胶囊能提高TAC生物利用度及安全性。限于纳入研究的质量和数量，上述结论仍需进一步研究佐证。更多还原

【Abstract】 Objective The effect of the Wuzhi Capsules on the plasma concentration,pharmacokinetic parameters of tacrolimus（TAC）,and liver and kidney function were systematically evaluated.Methods In major Chinese and English databases both do mestically and internationally,a systematic search was conducted on randomized controlled trials （RCTs） and prospective selfcontrol studies of TAC combined with Wuzhi Capsules in the treatment of liver transplant recipients.The search deadline was as of January 2023.Two rese archers independently completed research retrieval,data extraction,and methodological quality evaluation based on the inclusion and exclusion criteria of the research literature.Meta analysis was conducted on the blood drug concentration,liver and kidney function,and pharmacokinetic parameters of TAC i n liver transplant recipients after the combined application of Wuzhi Capsules.Results Eight articles were finally included,for a total of 381 liver transplant recipients.Meta-analysis results:compared with no combined Wuzhi Capsules，①after 1 month and 2 months of TAC combined with the Wuzhi Capsules,the plasma concentration of TAC in liver transplant recipients were[SMD=0.83,95%CI（0.34,1.31）,P=0.000 8],[SMD=0.57,95%CI（0.17,0.97）,P=0.005],respectively,the difference is statistically significant;There was no significant difference after 3 months and 6 months；②pharmacokinetic parameters:after combining Wuzhi Capsules,area under curve(AUC_0→t) of TAC in liver transplant recipients was[SMD=1.97,95%CI（1.27,2.66）,P<0.000 01],peak time(T_max) was[SMD=-0.85,95%CI（-1.45,-0.25）,P=0.005],peak concentration(C_max) was[SMD=1.79,95%CI（0.82,2.75）,P=0.000 3],the differences were all statistically significant；③after combining TAC and Wuzhi Capsules,alanine aminotransferase（ALT） was[SMD=-1.03,95%CI（-1.80,-0.25）,P=0.010],with significant difference.There was no significant difference in total bilirubin（TB） and serum creatinine（Cr）.Conclusion Liver transplant recipients received TAC-based related immunosuppression regimen in combination with the use of Wuzhi Capsules can achieve higher plasma concentration of TAC in the early stage of medication,and long-term medication does not affect the steady-state concentration of TAC in liver transplant recipients.In addition,combining Wuzhi Capsules can improve liver function in liver transplant recipients to some extent without affecting renal function and bile excretion.In terms of pharmacokinetics,Wuzhi Capsules can improve the bioavailability and safety of TAC.Limited to the quality and quantity of the included studies,the above conclusions still need further research and support.更多还原