Yamaguchi Kazunori, Fukuoka Noriyasu, Kimura Sumio, Shinohara Naoki, Tatsumichi Takakiyo, Tai Tatsuya, Kosaka Shinji, Ohnishi Hiroaki, Houchi Hitoshi
Department of Pharmacy, Kagawa University Hospital, Japan.
Yakugaku Zasshi. 2012;132(7):845-8. doi: 10.1248/yakushi.132.845.
We report a case of encephalopathy seemingly caused by tacrolimus (FK506) in spite of blood concentration near the upper limit of therapeutic range. A 26-year-old man received FK506 to prevent acute graft-versus-host disease after hematopoietic stem cell transplantation. He underwent an intravenous injection of FK506 the day before transplantation (day -1). He developed headache, hypertension, nausea and vomiting from day 2 to day 3. A computed tomography scan showed a low density area with unclear border in the bilateral cerebellar hemispheres. Thereafter, these symptoms improved with discontinuation of FK506, which was strongly suggestive of encephalopathy caused by FK506. The blood concentration of FK506 at the onset of encephalopathy was 21.7 ng/mL. Although this value was slightly higher than the standard therapeutic range (10-20 ng/mL), it was within clinically acceptable range in the early stage after stem cell transplantation. This indicates that even if the blood concentration of FK506 is within the therapeutic range, encephalopathy may develop. In summary, although the blood concentration of FK506 is useful as an indicator for prevention of encephalopathy, we propose careful monitoring not only of the blood concentration but also clinical status for the detection of initial symptoms and prevention of aggravation.
我们报告一例尽管他克莫司（FK506）血药浓度接近治疗范围上限，但仍似乎由其引起的脑病病例。一名26岁男性在造血干细胞移植后接受FK506以预防急性移植物抗宿主病。移植前一天（-1天）他接受了FK506静脉注射。从第2天到第3天，他出现头痛、高血压、恶心和呕吐。计算机断层扫描显示双侧小脑半球有边界不清的低密度区。此后，停用FK506后这些症状有所改善，这强烈提示FK506引起的脑病。脑病发作时FK506的血药浓度为21.7 ng/mL。虽然该值略高于标准治疗范围（10 - 20 ng/mL），但在干细胞移植后的早期仍处于临床可接受范围内。这表明即使FK506血药浓度在治疗范围内，也可能发生脑病。总之，虽然FK506血药浓度可作为预防脑病的指标，但我们建议不仅要仔细监测血药浓度，还要密切关注临床状况，以便检测初始症状并预防病情加重。
