Pharmacokinetics for once-daily modified release formulation of tacrolimus hydrate in unrelated hematopoietic stem cell transplantation
Pharmacokinetics for once-daily modified release formulation of tacrolimus hydrate in unrelated hematopoietic stem cell transplantation
复制标题
每日一次的他克莫司水合物缓释制剂在非亲缘造血干细胞移植中的药代动力学
作者：
S. Yano;S. Mori;Takeshi Saito;H. Yokoyama;Tomohito Machishima;T. Shimada;Y. Yahagi;K. Sugiyama;Y. Ogasawara;S. Takahara;K. Kasama;Atsushi Katsube;Y. Kamiyama;Kazuhito Suzuki;Yumiko Inui;N. Usui;K. Aiba;T. Yamashita
针对他克莫司的非依从性问题，研制了一种每日一次的他克莫司口服制剂(Tac QD)。然而，目前还没有关于从静脉注射Tac转换为Tac qd的疗效的数据。异基因造血干细胞移植(allo-SCT)。我们分析了Tac qd在allo-SCT受者中的药代动力学(PK)。共纳入10例接受非血缘关系供者异基因干细胞移植的恶性血液病患者。2例患者接受Tac静脉注射。移植前每天0.03 mg/kg。TAC静脉注射的管理。当患者从方案相关的胃肠道毒性中恢复并能耐受口服药物时，以1：4的比例转换为Tac qd。转换后，10名患者中有6名(60%)显示Tac暴露持续减少，需要调整剂量。从Tac i.v.TAC QD应在严密的医疗监督下进行。曲线下面积(AUC)与Tac QD谷值呈正相关，谷值应维持在7.5 ng/ml以上才能提供足够的AUC。虽然4名患者接受了HLADRB1抗原不匹配的非亲缘供者的骨髓，但没有患者出现III-IV级急性移植物抗宿主病(GVHD)。将Tac Qd修改为全血谷浓度维持在7.5 ng/ml以上可能与Tac Bid同样有效。
A once-daily modified release formulation of oral tacrolimus (Tac QD) has been developed in response to the problem of nonadherence. However, there have been no data available about the efficacy of Tac QD conversion from intravenous Tac (Tac i.v.) in allogeneic hematopoietic stem cell transplantation (allo-SCT). We analyzed the pharmacokinetics (PK) of Tac QD in allo-SCT recipients. A total of 10 patients with hematological malignancies who received allo-SCT from unrelated donors were enrolled. Patients received Tac i.v. at 0.03 mg/kg a day before transplantation. Administration of Tac i.v. was converted to Tac QD at a 1:4 ratio when the patients had recovered from regimen-related gastrointestinal toxicity and could tolerate oral medication. After conversion, six out of 10 patients (60 %) showed a sustained decrease in Tac exposure and required dose adjustment. The conversion from Tac i.v. to Tac QD should be performed under close medical supervision. Area under the curve (AUC) and the trough of Tac QD showed a correlation, and the trough should be maintained above 7.5 ng/ml to provide an adequate AUC. Although four patients received bone marrow from an HLA DRB1 1 antigen-mismatched unrelated donor, no patients developed grade III–IV acute graft-versus-host disease (GVHD). The modification of Tac QD to maintain a whole-blood trough concentration above 7.5 ng/ml may be as effective as Tac BID.
影响因子：
4.3
作者：
Perkins, Janelle;Field, Teresa;Anasetti, Claudio
通讯作者：
Anasetti, Claudio