静脉输注芬太尼对接受造血干细胞移植患者他克莫司血药浓度无影响。

Intravenous Infusion of Fentanyl Has No Effect on Blood Concentration of Tacrolimus in Patients Receiving Hematopoietic Stem-Cell Transplantation.

机构信息

Department of Pharmacy, Medical Hospital, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

出版信息

Ther Drug Monit. 2021 Oct 1;43(5):688-691. doi: 10.1097/FTD.0000000000000853.

DOI:10.1097/FTD.0000000000000853

PMID:33298744

Abstract

BACKGROUND

Both tacrolimus (TAC) and fentanyl are frequently used in patients receiving allogeneic hematopoietic stem-cell transplantation. A recently published report demonstrated that fentanyl can reduce the total body clearance of TAC; however, most patients in this study were administered concomitantly with azole antifungal agents, which are known to be strong inhibitors of CYP3A. Hence, the exact effect of fentanyl on TAC pharmacokinetics was unclear. In the current study, the authors retrospectively investigated the pharmacokinetic interaction between TAC and fentanyl in patients who were not concomitantly administered drugs that affect TAC metabolism.

METHODS

Patients with continuous infusion of TAC and fentanyl after hematopoietic stem-cell transplantation at the Tokyo Medical and Dental University between January 2014 and December 2018 were enrolled. The total body clearance of TAC was compared before and after the initiation or discontinuation of fentanyl.

RESULTS

Thirty patients (24 men and 6 women; median age, 11 years) were screened for their eligibility. Twenty-eight patients were enrolled for evaluating the effects of the fentanyl initiation on TAC pharmacokinetics; 2 patients were excluded because of the absence of data related to the TAC blood concentrations or the concomitant use of azole antifungals. Twenty patients were enrolled for investigating the effects of fentanyl discontinuation on TAC pharmacokinetics, whereas 10 patients were excluded because of the absence of data related to the blood concentration of TAC or the additional administration of azole antifungals. Furthermore, the total body clearance of TAC was not significantly affected by the initiation or discontinuation of fentanyl, although there were large interindividual variations. In addition, the results remained the same even when the analysis was performed independently for adults and children.

CONCLUSIONS

Intravenous infusion of fentanyl does not affect the pharmacokinetics of TAC.

摘要

背景

他克莫司（TAC）和芬太尼常用于接受异基因造血干细胞移植的患者。最近发表的一份报告表明，芬太尼可以降低 TAC 的全身清除率；然而，该研究中的大多数患者同时使用唑类抗真菌药物，这些药物已知是 CYP3A 的强抑制剂。因此，芬太尼对 TAC 药代动力学的确切影响尚不清楚。在目前的研究中，作者回顾性调查了在未同时给予影响 TAC 代谢的药物的造血干细胞移植后接受 TAC 和芬太尼持续输注的患者中 TAC 和芬太尼之间的药代动力学相互作用。

方法

纳入 2014 年 1 月至 2018 年 12 月期间在东京医科齿科大学接受造血干细胞移植后持续输注 TAC 和芬太尼的患者。比较芬太尼开始或停用前后 TAC 的全身清除率。

结果

对 30 名患者（24 名男性和 6 名女性；中位年龄 11 岁）进行了筛选，以评估其入选资格。纳入 28 名患者评估芬太尼起始对 TAC 药代动力学的影响；排除 2 名患者，因为 TAC 血药浓度相关数据或同时使用唑类抗真菌药物。纳入 20 名患者研究芬太尼停药对 TAC 药代动力学的影响，排除 10 名患者，因为 TAC 血药浓度相关数据或额外使用唑类抗真菌药物。此外，尽管个体间存在较大差异，但 TAC 的全身清除率不受芬太尼开始或停用的影响。此外，即使分别对成人和儿童进行分析，结果也保持不变。