影响造血干细胞移植患者他克莫司血药浓度的因素分析
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摘要
目的探讨造血干细胞移植患者口服他克莫司血药浓度影响因素及变化规律。方法收集本院94例口服他克莫司造血干细胞移植患者的病历资料,入选的患者口服他克莫司需达到稳态血药浓度,每日(0. 05±0. 03) mg·kg~(-1),给药间隔12,24 h。用微粒子酶免疫分析法测定他克莫司全血的血药浓度。对他克莫司稳态谷浓度和性别、年龄、生化指标及合并用药进行相关性分析。结果男性组和女性组的他克莫司标准化血药浓度分别为(222. 47±147. 05),(165. 93±88. 88) ng·m L~(-1)·mg~(-1)·kg,组间比较差异有统计学意义(P <0. 01);红细胞压积与他克莫司标准化血药浓度呈正相关(r=0. 27,P <0. 01)。结论性别和红细胞压积能显著影响造血干细胞移植患者他克莫司标准化血药浓度。
Objective To investigate the influence factors of tacrolimus blood concentration in patients undergoing hematopoietic stem cell transplantation. Methods Data of tacrolimus usage were retrospectively collected in 94 patients undergoing hematopoietic stem cell transplantation in our hospital. The patients were required to take tacrolimus( 0. 05 ± 0. 03) mg·kg~(-1) orally once or twice a day to reach the steady-state blood concentration. Microparticle enzyme immunoassay was used to determine tacrolimus whole-blood concentrations. Association of sex,age,corresponding biochemical testing values and drug combination with tacrolimus blood concentrations were analyzed. Results Dose-adjusted concentration of male group and female group were( 222. 47 ± 147. 05)ng·m L~(-1)·mg~(-1)·kg and( 165. 93 ± 88. 88) ng·m L~(-1)·mg~(-1)·kg,respectively. The differences between two groups were statistically significant( P < 0. 01). There was a positive correlation between the hematocrit and tacrolimus dose-adjusted concentration( r = 0. 27,P < 0. 01).Conclusion Sex and hematocrit can significantly affect tacrolimus dose-adjusted concentration.
Objective To investigate the influence factors of tacrolimus blood concentration in patients undergoing hematopoietic stem cell transplantation. Methods Data of tacrolimus usage were retrospectively collected in 94 patients undergoing hematopoietic stem cell transplantation in our hospital. The patients were required to take tacrolimus( 0. 05 ± 0. 03) mg·kg~(-1) orally once or twice a day to reach the steady-state blood concentration. Microparticle enzyme immunoassay was used to determine tacrolimus whole-blood concentrations. Association of sex,age,corresponding biochemical testing values and drug combination with tacrolimus blood concentrations were analyzed. Results Dose-adjusted concentration of male group and female group were( 222. 47 ± 147. 05)ng·m L~(-1)·mg~(-1)·kg and( 165. 93 ± 88. 88) ng·m L~(-1)·mg~(-1)·kg,respectively. The differences between two groups were statistically significant( P < 0. 01). There was a positive correlation between the hematocrit and tacrolimus dose-adjusted concentration( r = 0. 27,P < 0. 01).Conclusion Sex and hematocrit can significantly affect tacrolimus dose-adjusted concentration.
引文
[1] SHINGAKI S,TSUKADA N,IKEDA M,et al. Graft-versus-host disease free,relapse-free survival after HLA-identical sibling peripheral blood stem cell transplantation with tacrolimus-based graft-versus-host disease prophylaxis in Japanese patients[J]. Transplant Proc,2018,50(1):241-245.
[2]宋艳,成璐,贾淼鑫,等.肾病综合征患者他克莫司血药浓度监测的回顾性分析与评价[J].中国医院药学杂志,2017,37(7):654-658.
[3] COTREAU M M,VON MOLTKE L L,GREENBLATT D J. The influence of age and sex on the clearance of cytochrome P450 3A substrates[J]. Clin Pharmacokinet,2005,44(1):33-60.
[4] MEKKI Q,LEE C,AWEEKA F,et al. Pharmacokinetics of tacrolimus(FK 506)in kidney transplant patients[J]. Clin Pharmacol Ther,1993,53(3):238.
[5] MORI T,KATO J,YAMANE A,et al. Drug interaction between voriconazole and tacrolimus and its association with the bioavailability of oral voriconazole in recipients of allogeneic hematopoietic stem cell transplantation[J]. Int J Hematol,2012,95(5):564-569.
[6] TRIFILIO S,ORTIZ R,PENNICK G,et al. Voriconazole therapeutic drug monitoring in allogeneic hematopoietic stem cell transplant recipients[J]. Bone Marrow Transplant,2005,35(5):509-513.
[7] HESSELINK D A,VAN SCHAIK R H,VAN DER HEIDEN I P,et al. Genetic polymorphisms of the CYP3A4,CYP3A5,and MDR-1genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus[J]. Clin Pharmacol Ther,2003,74(3):245-254.
[2]宋艳,成璐,贾淼鑫,等.肾病综合征患者他克莫司血药浓度监测的回顾性分析与评价[J].中国医院药学杂志,2017,37(7):654-658.
[3] COTREAU M M,VON MOLTKE L L,GREENBLATT D J. The influence of age and sex on the clearance of cytochrome P450 3A substrates[J]. Clin Pharmacokinet,2005,44(1):33-60.
[4] MEKKI Q,LEE C,AWEEKA F,et al. Pharmacokinetics of tacrolimus(FK 506)in kidney transplant patients[J]. Clin Pharmacol Ther,1993,53(3):238.
[5] MORI T,KATO J,YAMANE A,et al. Drug interaction between voriconazole and tacrolimus and its association with the bioavailability of oral voriconazole in recipients of allogeneic hematopoietic stem cell transplantation[J]. Int J Hematol,2012,95(5):564-569.
[6] TRIFILIO S,ORTIZ R,PENNICK G,et al. Voriconazole therapeutic drug monitoring in allogeneic hematopoietic stem cell transplant recipients[J]. Bone Marrow Transplant,2005,35(5):509-513.
[7] HESSELINK D A,VAN SCHAIK R H,VAN DER HEIDEN I P,et al. Genetic polymorphisms of the CYP3A4,CYP3A5,and MDR-1genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus[J]. Clin Pharmacol Ther,2003,74(3):245-254.