Department of Nephrology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
J Heart Lung Transplant. 2011 Sep;30(9):1003-10. doi: 10.1016/j.healun.2011.02.008. Epub 2011 Apr 13.
A prolonged-release formulation of tacrolimus for once-daily administration (tacrolimus QD) has been developed. This phase II, open-label, multicenter, prospective single-arm study compared the pharmacokinetics (PK) of tacrolimus in stable heart transplant patients before and after conversion from twice-daily tacrolimus (tacrolimus BID) to tacrolimus QD.
Heart transplant recipients (≥6 months after transplant), previously maintained on tacrolimus BID-based therapy, received tacrolimus BID from Days 1 to 7 and were converted on a 1:1 (mg/mg) basis to tacrolimus QD. Five 24-hour PK profiles were collected (Days 1, 7, 8, 14, 21). Safety parameters were also evaluated.
Of 85 patients, 45 (50.6%) completed all 5 evaluable PK profiles. Steady-state tacrolimus area under the curve, 0 to 24 hours (AUC(0-24)) and minimum concentration (C(min)) were comparable for both formulations, with treatment ratio means of 90.5% (90% confidence intervals [CI], 86.4%-94.6%) and 87.4% (95% CI, 82.9%-92.0%), respectively (acceptance interval, 80%-125%). There was good correlation between AUC(0-24) and C(min) for tacrolimus QD (r = 0.94) and BID (r = 0.91). The relationship between these 2 parameters was also similar.
This study provides evidence for successful conversion from tacrolimus BID to QD on a 1:1 (mg/mg) total daily dose basis. Approximately one-third of patients may require dose adjustments. Both formulations were well tolerated, with stable renal function during the study. Adverse events were reported by approximately one-tenth of patients receiving tacrolimus BID and a quarter of those who received QD.
已开发出一种用于每日一次给药的他克莫司延长释放制剂（他克莫司 QD）。这项 II 期、开放性、多中心、前瞻性单臂研究比较了在从每日两次的他克莫司（他克莫司 BID）转换为他克莫司 QD 之前和之后，稳定的心脏移植受者的他克莫司的药代动力学（PK）。
心脏移植受者（移植后≥6 个月），先前接受基于他克莫司 BID 的治疗，在第 1 天至第 7 天接受他克莫司 BID，并以 1:1（mg/mg）的比例转换为他克莫司 QD。采集了 5 个 24 小时 PK 曲线（第 1、7、8、14、21 天）。还评估了安全性参数。
在 85 名患者中，45 名（50.6%）完成了所有 5 个可评估的 PK 曲线。两种制剂的稳态他克莫司 AUC0-24 和最小浓度（Cmin）相当，治疗比均值分别为 90.5%（90%置信区间[CI]，86.4%-94.6%）和 87.4%（95%CI，82.9%-92.0%）（接受区间，80%-125%）。他克莫司 QD（r=0.94）和 BID（r=0.91）的 AUC0-24 与 Cmin 之间具有良好的相关性。这两个参数之间的关系也相似。
这项研究提供了在 1:1（mg/mg）总日剂量基础上从他克莫司 BID 成功转换为 QD 的证据。大约三分之一的患者可能需要调整剂量。两种制剂均耐受良好，研究期间肾功能稳定。大约十分之一接受他克莫司 BID 的患者和四分之一接受 QD 的患者报告了不良反应。
