Chronopharmacokinetics of tacrolimus in kidney transplant recipients: Occurrence of acute rejection
Chronopharmacokinetics of tacrolimus in kidney transplant recipients: Occurrence of acute rejection
复制标题
DOI：
10.1177/0091270003254797
复制
发表时间：
2003-08-01
影响因子：
2.9
通讯作者：
Suzuki, T
中科院分区：
文献类型：
--
作者：
Tada, H;Satoh, S;Suzuki, T
研究了16例成人肾移植术后1个月他克莫司临床药代动力学的昼夜变化。接受者每天两次（上午9点和晚上9点）给予他克莫司，并在口服给药前和口服给药后1、2、3、6、9和12小时采集全血样本。移植后第28天采用同种异体肾核活检法采集移植肾组织标本。浓度-时间曲线下的面积（AUC(0-12)）（白天214 ng.h/mL，夜间223 ng.h/mL）没有昼夜节律变化。夜间给药后，平均停留时间（MRT0-12）和到达峰值浓度时间（t(max)）略有延迟，但无统计学意义。3例患者（18.8%）在移植后4 ~ 6周发生临床急性排斥反应（AR），有AR患者夜间AUC（0 ~ 12）明显低于无AR患者（平均18.4%）。有AR患者和无AR患者之间的最大浓度（C-max）或早晚最低水平无统计学意义。各采样时间托克莫司浓度与AUC（0 ~ 12）的相关性。晨槽浓度与日间AUC（0 ~ 12）的相关性较差（r(2) = 0.125），与夜间AUC（0 ~ 12）的相关性较弱（r(2) = 0.424）。晨给药后2、3、6小时（C-2、C-3、C-6）他克莫司浓度与日间AUG有较好的相关性。本研究结果提示肾移植患者他克莫司临床药代动力学在白天和夜间的差异不显著，而夜间较低的AUG与AR的发生相对应。
The circadian variation of clinical pharmacokinetics of tacrolimus was studied using 16 adult renal transplant recipients 1 month after the operation. The recipients were administered tacrolimus twice a day(9 a.m. and 9 p.m.), and whole-blood samples were obtained just prior to and 1, 2, 3, 6, 9, and 12 hours after oral administration. Histological specimens of transplant kidney were collected by on allograft core biopsy on day 28 after the transplantation. There were no circadian changes in the area under the concentration-time curve (AUC(0-12)) (214 ng.h/mL during daytime vs. 223 ng.h/mL during nighttime) resulting from morning and night doses. A slight delay in mean residence time (MRT0-12) and time to the peak concentration (t(max)) was found after night doses, but there was no statistical significance. Three patients (18.8%) had a clinical acute rejection (AR) episode 4 to 6 weeks after transplantation, and AUC(0-12) at nighttime was significantly lower (18.4 % on average) in patients with AR in comparison to those without AR. There was no statistical significance in maximum concentration (C-max) or morning/night trough levels between patients with and without AR, In regard to the correlation between tocrolimus concentrations in each sampling time and AUC(0-12), the morning trough concentrations were less predictable for daytime AUC(0-12) (r(2) = 0.125), but there was a weak correlation to nighttime AUC(0-12) (r(2) = 0.424). Tacrolimus concentrations at 2, 3, and 6 hours after the morning dose (C-2, C-3, and C-6) had a good correlation against daytime AUG. The results of this study indicate that the variance on the clinical phormacokinetics of tacrolimus between daytime and nighttime in renal transplant patients is not significant, while the lower nighttime AUG corresponded to the occurrence of AR.