Department of Pharmacy, The First Affiliated Hospital of Soochow University, Soochow University , Suzhou , China.
Expert Opin Drug Metab Toxicol. 2019 Oct;15(10):803-811. doi: 10.1080/17425255.2019.1675635. Epub 2019 Oct 9.
: Graft-versus-host disease (GVHD) is the most common complication of hematopoietic stem cell transplantation (HSCT); therefore, the prevention of GVHD is important for a successful treatment. Tacrolimus (Tac), a calcineurin inhibitor, has been widely used for the prophylaxis of GVHD in HSCT recipients. : This review introduces phase II/III of clinical trials related with Tac's roles in the prevention of GVHD in HSCT. Furthermore, we discuss the normal ranges of Tac concentrations, pharmacogenetics, and drug interactions of Tac, as well as its side effects in adult HSCT recipients. : A series of studies has established the efficacy and safety of Tac alone or in combination with other agents in HSCT. However, successful administration of Tac is complicated by its narrow therapeutic window, inter-patient pharmacokinetic variability, and a spectrum of undesirable side effects. It is necessary to maintain concentrations of Tac within the desired ranges for GVHD prophylaxis. Moreover, various factors contribute to significant variability in Tac pharmacokinetics, including drug interactions and genomic variation.
移植物抗宿主病（GVHD）是造血干细胞移植（HSCT）最常见的并发症；因此，预防 GVHD 对于成功治疗至关重要。他克莫司（Tac），一种钙调神经磷酸酶抑制剂，已广泛用于 HSCT 受者 GVHD 的预防。
本综述介绍了 Tac 在 HSCT 预防 GVHD 中的作用的 II/III 期临床试验。此外，我们讨论了 Tac 的浓度、药物遗传学和药物相互作用的正常范围，以及其在成人 HSCT 受者中的副作用。
一系列研究已经证实了 Tac 单独或与其他药物联合使用在 HSCT 中的疗效和安全性。然而， Tac 的成功给药受到其狭窄的治疗窗、个体间药代动力学变异性和一系列不良副作用的影响。需要将 Tac 的浓度维持在预防 GVHD 的理想范围内。此外，多种因素导致 Tac 药代动力学的显著变异性，包括药物相互作用和基因组变异。
