Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Am J Transplant. 2013 Aug;13(8):2191-7. doi: 10.1111/ajt.12274. Epub 2013 Jun 4.
The pharmacokinetics, efficacy and safety of once-daily tacrolimus formulation (Tac-OD) were assessed in 34 stable pediatric kidney transplant recipients. Enrolled patients received their dose of twice-daily tacrolimus formulation (Tac-BID) on study Days 0 through 7. On the morning of study Day 8, the total daily doses for patients were converted to Tac-OD on a 1:1 basis and maintained on a once-daily morning dosing regimen. Tacrolimus pharmacokinetic profiles were obtained on study Days 7, 14 and 28 (after dose adjustment). Although the mean C0 concentrations (4.10 ± 1.16-3.53 ± 1.10 ng/mL, p = 0.004), and AUC0-24 (151.8 ± 41.6-129.8 ± 39.3 ng h/mL, p < 0.001) were decreased significantly after a 1:1 based conversion, there was high interindividual variability. The dose of Tac-OD was decreased in 26.5% and increased in 44.1% of patients. The resultant tacrolimus dose and pharmacokinetic profiles on study Day 28 were comparable to those on Day 7. There were no serious adverse events. In conclusion, Tac-BID can be safely converted to Tac-OD in stable pediatric kidney transplant patients with the heightened therapeutic drug monitoring. Effects of drug conversion on the cardiovascular risk factors, neurological side effects and adherence should be further evaluated.
在 34 名稳定的儿科肾移植受者中评估了每日一次他克莫司制剂（Tac-OD）的药代动力学、疗效和安全性。入组患者在研究第 0 天至第 7 天接受每日两次他克莫司制剂（Tac-BID）的剂量。在研究第 8 天的早晨，根据 1:1 的比例将患者的每日总剂量转换为 Tac-OD，并维持每日一次的早晨给药方案。在研究第 7、14 和 28 天（剂量调整后）获得他克莫司药代动力学曲线。虽然平均 C0 浓度（4.10 ± 1.16-3.53 ± 1.10 ng/mL，p = 0.004）和 AUC0-24（151.8 ± 41.6-129.8 ± 39.3 ng h/mL，p < 0.001）在基于 1:1 的转换后显著降低，但个体间变异性很大。26.5%的患者减少了 Tac-OD 的剂量，44.1%的患者增加了 Tac-OD 的剂量。研究第 28 天的他克莫司剂量和药代动力学曲线与第 7 天相当。没有严重的不良事件。总之，在进行强化治疗药物监测的稳定儿科肾移植患者中，Tac-BID 可安全转换为 Tac-OD。药物转换对心血管危险因素、神经副作用和依从性的影响应进一步评估。
