Early application of tacrolimus extended-release capsule after kidney transplantation
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摘要:
目的 探讨肾移植术后早期应用他克莫司缓释胶囊（Tac-ER）的有效性及安全性。 方法 回顾性分析接受34对供肾所行肾移植的68例受者临床资料，接受同一供者两侧肾脏的2例受者术后分别采用Tac-ER（Tac-ER组）和他克莫司胶囊（Tac-IR）（Tac-IR组）作为基础免疫抑制药之一。比较两组他克莫司剂量及血药浓度变化、药物浓度个体内变异度（IPV）、肾功能、急性排斥反应发生率、受者和移植物存活率、不良事件发生情况。 结果 Tac-ER组的平均他克莫司日剂量高于Tac-IR组（F=8.386，P=0.005）。Tac-ER组术后4 d平均谷浓度未达目标浓度，为（6.14±4.04）ng/mL，低于Tac-IR组的（9.41±5.47）ng/mL（F=7.854，P=0.007）。Tac-ER组术后1个月内他克莫司谷浓度IPV高于Tac-IR组（0.44±0.15比0.36±0.12，P=0.032）。术后第6个月时，Tac-ER组和Tac-IR组肾功能比较差异无统计学意义[血清肌酐为（126±26）μmol/L比（120±28）μmol/L，估算肾小球滤过率为（56±13）mL/（min·1.73 m2）比（60±15）mL/（min·1.73 m2），均为P > 0.05]。两组移植物和受者存活率均为100%。Tac-ER组和Tac-IR组急性排斥反应均于术后1个月内发生，发生率分别为18%和3%，差异无统计学意义（P > 0.05）。Tac-ER组和Tac-IR组不良事件总发生率分别为94%和97%，差异无统计学意义（P > 0.05）。 结论 Tac-ER的有效性和安全性与Tac-IR相似，但需要口服更高剂量才能达到与Tac-IR相似的血药浓度。初始应用Tac-ER应在术前提前口服或以负荷剂量作为首剂量，以提高术后早期他克莫司的全身暴露量，预防暴露不足导致的急性排斥反应。 Abstract:Objective To evaluate the efficacy and safety of tacrolimus extended-release (Tac-ER) in the early stage after kidney transplantation. Methods Clinical data of 68 recipients undergoing kidney transplantation from 34 pairs of renal allografts were retrospectively analyzed. Two recipients who received bilateral kidneys from the same donor were treated with Tac-ER (Tac-ER group) and tacrolimus immediate-release (Tac-IR) (Tac-IR group) as one of the basic immunosuppressant. The changes of tacrolimus dosage and blood concentration, intra-patient variability (IPV), renal function, incidence of acute rejection, recipient and allograft survival rates and adverse events were statistically compared between two groups. Results The average daily dose of tacrolimus in the Tac-ER group was significantly higher than that in the Tac-IR group (F=8.386, P=0.005). In the Tac-ER group, the mean trough concentration at postoperative 4 d was (6.14±4.04) ng/mL, did not reach the target concentration, significantly lower than (9.41±5.47) ng/mL in the Tac-IR group (F=7.854, P=0.007). In the Tac-ER group, the IPV of trough concentration of tacrolimus within postoperative 1 month was significantly higher than that in the Tac-IR group (0.44±0.15 vs. 0.36±0.12, P=0.032). At postoperative 6 months, there was no significant difference in the renal function between two groups [serum creatinine level was (126±26) μmol/L vs. (120±28) μmol/L, and the estimated glomerular filtration rate was (56±13) mL/(min·1.73 m2) vs. (60±15) mL/(min·1.73 m2), both P > 0.05]. The allograft and recipient survival rates were 100% in both groups. The incidence of acute rejection within postoperative 1 month was 18% in the Tac-ER group and 3% in the Tac-IR group, with no significant difference (P > 0.05). The overall incidence of adverse events was 94% in the Tac-ER group and 97% in the Tac-IR group, with no significant difference (P > 0.05). Conclusions The efficacy and safety of Tac-ER are equivalent to those of Tac-IR, whereas a higher dose of Tac-ER should be orally given to reach the blood concentration similar to that of Tac-IR. During early-stage drug treatment, Tac-ER should be orally given before kidney transplantation or inittally with loading dose, aiming to increase the systemic exposure to tacrolimus early after kidney transplantation and prevent acute rejection caused by insufficient exposure. -
图 1 两组受者他克莫司日剂量及谷浓度水平
注：与Tac-IR组比较，aP < 0.05。
Figure 1. Daily dose and trough concentration of tacrolimus of recipients in two groups
图 2 快代谢型受者他克莫司日剂量及谷浓度水平
注：与Tac-IR组比较，aP < 0.05。
Figure 2. Daily dose and trough concentration level of tacrolimus in fast metabolizing recipients
图 3 慢代谢型受者他克莫司日剂量及谷浓度水平
注：与Tac-IR组比较，aP < 0.05。
Figure 3. Daily dose and trough concentration level of tacrolimus in slow metabolizing recipients
图 4 两组受者血清肌酐和eGFR水平比较
Figure 4. Comparison of serum creatinine and eGFR levels of recipients between two groups
表 1 两组受者他克莫司谷浓度IPV比较
Table 1. Comparison of the IPV of tacrolimus trough concentration in recipients between two groups (x±s)
变量 Tac-ER组（n=34） Tac-IR组（n=34） P值 IPV 术后1个月 0.44±0.15 0.36±0.12 0.032 术后1~6个月 0.18±0.02 0.26±0.15 0.055 快代谢型IPV 术后1个月 0.43±0.15 0.32±0.10 0.015 术后1~6个月 0.11±0.07 0.24±0.10 0.007 慢代谢型IPV 术后1个月 0.45±0.15 0.39±0.13 0.307 术后1~6个月 0.19±0.08 0.27±0.15 0.190 
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