医学
他克莫司
优势比
泼尼松龙
内科学
霉酚酸
曲线下面积
肾移植
霉酚酸酯
加药
可能性
移植
泌尿科
钙调神经磷酸酶
逻辑回归
免疫抑制
肾功能
肾
免疫抑制剂
肾病科
硫唑嘌呤
药代动力学
肌酐
治疗药物监测
作者
Katherine A. Barraclough,Christine E. Staatz,David W. Johnson,Katie J. Lee,Brett McWhinney,Jacobus P.J. Ungerer,Carmel M. Hawley,Scott B. Campbell,D. R. Leary,Nicole M. Isbel
标识
DOI:10.1111/j.1432-2277.2012.01553.x
摘要
This study analysed associations between tacrolimus, mycophenolic acid (MPA) and prednisolone exposures on day 4 and month 1 post kidney transplant and clinical outcomes. Area under the concentration-time curve (AUC) for each drug was estimated using validated multiple regression-derived limited sampling strategies. Multivariate logistic regression was used to associate drug exposure with clinical outcomes. One hundred and twenty subjects were studied. Between-subject variability in dose-adjusted exposure to each medication was high. Both day 4 tacrolimus and MPA exposures were independently predictive of delayed graft function (2.6 change in odds for a standard deviation (SD) increase in tacrolimus AUC(0-12) , P = 0.02; 0.23 change in odds for a SD increase in MPA AUC(0-12) , P = 0.02). Both day 4 MPA and total prednisolone exposures were independently predictive of rejection (0.20 change in odds for a SD increase in MPA AUC(0-12) , P = 0.04; 0.40 change in odds for a SD increase in total prednisolone AUC(0-6) , P = 0.03). Lowest tertile exposure to all three immunosuppressant medications imposed significantly higher odds of rejection [adjusted odds ratio 34.2 (95% CI 4.1, 284.4), P = 0.001]. This study highlights the importance of achieving early target exposure and suggests a potential role for individualized initial dosing or early therapeutic monitoring of all three immunosuppressive agents.
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