Yano Shingo, Mori Shinichiro, Saito Takeshi, Yokoyama Hiroki, Machishima Tomohito, Shimada Takaki, Yahagi Yuichi, Sugiyama Katsuki, Ogasawara Yoji, Takahara Shinobu, Kasama Kinuyo, Katsube Atsushi, Kamiyama Yutaro, Suzuki Kazuhito, Inui Yumiko, Usui Noriko, Aiba Keisuke, Yamashita Takuya
Division of Clinical Oncology and Hematology, Jikei University School of Medicine, 3-25-8 Nishi Shinbashi, Minatoku, Tokyo, 105-8461, Japan,
Ann Hematol. 2015 Mar;94(3):491-6. doi: 10.1007/s00277-014-2233-7. Epub 2014 Oct 19.
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.
为应对不依从问题，已研发出每日一次的口服他克莫司缓释制剂（他克莫司QD）。然而，关于在异基因造血干细胞移植（allo-SCT）中从静脉注射他克莫司（他克莫司i.v.）转换为他克莫司QD的疗效，尚无可用数据。我们分析了allo-SCT受者中他克莫司QD的药代动力学（PK）。总共纳入了10例接受无关供者allo-SCT的血液系统恶性肿瘤患者。患者在移植前一天接受0.03 mg/kg的他克莫司i.v.。当患者从与方案相关的胃肠道毒性中恢复且能够耐受口服药物时，将他克莫司i.v.的给药以1:4的比例转换为他克莫司QD。转换后，10例患者中有6例（60%）他克莫司暴露持续下降，需要调整剂量。从他克莫司i.v.转换为他克莫司QD应在密切的医学监督下进行。他克莫司QD的曲线下面积（AUC）和谷浓度显示出相关性，谷浓度应维持在7.5 ng/ml以上以提供足够的AUC。虽然4例患者接受了来自HLA DRB1 1抗原不匹配的无关供者的骨髓，但没有患者发生III-IV级急性移植物抗宿主病（GVHD）。将他克莫司QD调整以维持全血谷浓度高于7.5 ng/ml可能与他克莫司每日两次（Tac BID）一样有效。
