Przepiorka D, Blamble D, Hilsenbeck S, Danielson M, Krance R, Chan K W
Baylor College of Medicine Center for Cell and Gene Therapy, Houston, Texas 77030, USA.
Bone Marrow Transplant. 2000 Sep;26(6):601-5. doi: 10.1038/sj.bmt.1702588.
For prevention of graft-versus-host disease, the consensus initial intravenous dose of tacrolimus for adults is 0.03 mg/kg/day. Whether target whole blood concentrations of tacrolimus in children undergoing hematopoietic stem cell transplantation can be achieved reproducibly with this dose is not known. We reviewed the tacrolimus blood levels and calculated clearances for 55 children (aged 6 months to 18 years, median 9 years) using tacrolimus after allogeneic marrow, blood stem cell or cord blood transplantation. The tacrolimus dose regimen was 0.03 mg/kg/day by continuous infusion starting on day -1 or day -2. At the first sampling in the peritransplant period, 71% of the tacrolimus blood levels were within the target range of 5-15 ng/ml, 87% were in the safe range of 5-20 ng/ml, 9% were toxic, and 4% were subtherapeutic. Twenty-five children were converted to oral drug using the recommended oral/intravenous dose ratio of 4.0. At the first sampling after oral conversion, 80% were in the target range, and 20% were subtherapeutic. Clearance of tacrolimus was calculated from the blood levels for patients during intravenous dosing and normalized by ideal body weight. There was a decreased clearance over the first 2 weeks only for the children >12 years old (P = 0.014). The initial calculated clearances of tacrolimus did not differ between age groups, but at steady state the mean tacrolimus clearance (+/- s.d.) was higher for those <6 years old (0.159+/-0.082 l/h/kg) than for those 6-12 years old (0.109+/-0.053 l/h/kg) or >12 years old (0.104 +/-0.068 l/h/kg). Children <6 years old undergoing hematopoietic stem cell transplantation have a higher weight-normalized tacrolimus clearance than older children and adults, and careful therapeutic monitoring is needed in the first 2 weeks after transplantation to avoid prolonged subtherapeutic dosing for this age group.
为预防移植物抗宿主病，成人他克莫司的初始静脉给药共识剂量为0.03mg/kg/天。对于接受造血干细胞移植的儿童，使用该剂量是否能可重复地达到他克莫司的目标全血浓度尚不清楚。我们回顾了55名儿童（年龄6个月至18岁，中位年龄9岁）在接受异基因骨髓、血液干细胞或脐血移植后使用他克莫司的血药浓度，并计算了清除率。他克莫司的给药方案是从第-1天或第-2天开始持续输注，剂量为0.03mg/kg/天。在移植期首次采样时，71%的他克莫司血药浓度在5-15ng/ml的目标范围内，87%在5-20ng/ml的安全范围内，9%有毒性，4%低于治疗浓度。25名儿童按照推荐的口服/静脉剂量比4.0转换为口服给药。口服转换后的首次采样时，80%在目标范围内，20%低于治疗浓度。根据静脉给药期间患者的血药浓度计算他克莫司的清除率，并按理想体重进行标准化。仅12岁以上儿童在最初2周内清除率降低（P=0.014）。各年龄组他克莫司的初始计算清除率无差异，但在稳态时，<6岁儿童的他克莫司平均清除率（±标准差）（0.159±0.082l/h/kg）高于6-12岁儿童（0.109±0.053l/h/kg）或12岁以上儿童（0.104±0.068l/h/kg）。接受造血干细胞移植的<6岁儿童的他克莫司体重标准化清除率高于大龄儿童和成人，移植后前2周需要仔细进行治疗监测，以避免该年龄组出现长时间低于治疗浓度的给药情况。
