期刊文献+

用多重线性回归法研究他克莫司的群体表观清除率 被引量:2

Population pharmacokinetic estimation of tacrolimus apparent clearance through Multiple-Linear Regression
下载PDF
导出
摘要 [目的]用多重线性回归法估算肝移植术后患者他克莫司(FK506)的群体表观清除率,找出有显著影响的各种因素,并用建立表观清除率(CL/F)的群体模型。[方法]回顾性收集21例(男16例,女5例)肝移植患者他克莫司血药浓度监测值及患者的个体信息。分别以直接代入、取布尔值和取对数值3种方法处理数据后,用多重线性回归法建立统计学模型,再用未参与建模的外部数据5例(男4例,女1例)26个血样点进行预测,计算每个采样点的预测误差百分比(PE%)和绝对预测误差百分比(|PE|%)。[结果]经验证方法一直接代入和方法二取布尔值建立的模型都没实际意义,只有方法三取对数值建立的模型有意义,证明FK506的表观清除率与AST、ALB、GGT及术后时间(以周计)有关,与年龄、性别等因素无关。[结论]在充分考虑到各固定效应和随机效应的前提下,多重线性回归法也可以建立出优化的药代动力学群体模型为临床调整给药方案提供理论依据。 [ Objective] The goal was to estimate the value of tacrolimus apparent clearance (CI/F) in adult liver transplant recipients and found out the factors affecting CI/F as well as develop a population pharmacokinetic model for CI/F by statistical methods. [ Methods] Tacrolimus blood drug concentration and individual information were obtained from 21 liver transplant recipients (16 male and 5 female) retrospectively. Develop a population pharmacokinetic model for CI/F through three different methods, including introducing data directly, taking Boolean value, and taking In value. Hereafter, constructed model through multiple - linear regression provided by SPSS. Finally, introduced 5 external datasets (male 4 and female 1, including 26 simple points) into developed model to predict the value of CI/F, check errors between predicted values and measured values, and calculate prediction error percentage ( PE% ) and absolute prediction error percentage ( | PE% | ). [ Results ] The models from method one, introducing data directly, and method two, taking Boolean value are invalidation; only model from method three, taking In value, is available. It is proved that FK506 apparent clearance is related to AST, ALB, GGT and post - transplant time, while is independent to other factors, such as age and gender. [ Conclusion] If fixed effects and random effects have been taken into account adequately; optimized population pharmacokinetic model could be developed by multiple - linear regression, which would provide theoretical foundation for regulating dosage regimen in clinic.
出处 《大连医科大学学报》 CAS 2007年第6期535-538,共4页 Journal of Dalian Medical University
关键词 群体药物代谢动力学 他克莫司 多重线性回归 表观清除率 population pharmacokinetic tacrolimus (FK506) multiple - Linear regression apparent clearance
  • 相关文献

参考文献9

二级参考文献32

  • 1Undre NA, Schafer A. Factors affecting the pharmacokinetics of tacrolimus in the first year after renal transplantation. European Tacrolimus Multicentre Renal Study Group Transplantation Proc, 1998, 30(4): 1261.
  • 2David A, Askow L, Lavio F, et al. An open label, concentration ranging trial of FK506 in primary kidney transplantayion. Transplantation, 1996,62:900.
  • 3Undre NA, Stevenson P, Schafer A. Pharmacokinetics of tacrolimus:Clinically relevant aspects. Transplantation Proc, 1999, 31: 21s.
  • 4Ihara H, Shinkuma D, Ichikawa Y, et al. Intra- interindividual variation in the pharmacokinetics of tacrolimuss (FK506) in kidney transplant recipients- importance of trough level as a practical indicate. Int J Urol,1995, 2:151.
  • 5Venkataramanan R, Jain A, Warty VS, et al. Pharmacokinetics of FK506in transplant patients. Transplantation Proc, 1991,23:2736.
  • 6Undre NA, Stevenson P, Schafer A. Pharmacokinetics of tacrolinus:Clinically relevant aspects. Transplantation Proc, 1999, 31: 21s.
  • 7Mekki Q, Phd MD, Lee C, et al. Pharmacokinetics of Tacrolimus(FK506) in kidney transplant patients. Clin Pharamcol Ther, 1993, 54:238.
  • 8Mahalati K, Belitsky P, Kiberd B, et al. Absorption profiling- a novel method for monitoring neoral in kidney transplantation that reduces rejection and nephrotoxicity. Transplantation, 2000,69:s114.
  • 9Reith DM, Hooper WD, Parke J, et al. Population pharmacokinetic modeling of steady state carbamazapine clearance in children, adolescents, and adults[ J]. J pharmacokinet pharmacodynam,2001 ;28: 79- 92.
  • 10Venkataramanan R, Swaminathan A, Prasad T, et al. Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet, 1995, 29:404-430.

共引文献62

同被引文献21

引证文献2

二级引证文献5

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部