泊沙康唑对异基因造血干细胞移植受者环孢素血药浓度的影响

Effects of posaconazole on the plasma concentration of cyclosporine in recipients of allogeneic hematopoietic stem cell transplantation

目的:探讨异基因造血干细胞移植(allo-HSCT)受者体内泊沙康唑对环孢素血药浓度的影响。方法:纳入27例allo-HSCT受者,采用环孢素免疫抑制治疗且血药浓度位于治疗窗(150~300μg·L^(-1))内,之后合用泊沙康唑预防真菌感染。收集受者合用泊沙康唑前与合用1~10 d内的环孢素谷浓度(C_(0))、浓度剂量比(C_(0)/D),比较两药合用前后环孢素的剂量及浓度。结果:allo-HSCT受者合用泊沙康唑后,环孢素C_(0)显著升高,剂量校正后发现C_(0)/D在两药合用7~10 d增长最为显著(P<0.01);16例研究期间环孢素C_(0)均位于治疗窗的受者,环孢素的日剂量由合用前的(2.55±0.80)mg·kg^(-1)于合用7~10 d降至(1.61±0.43)mg·kg^(-1),约降低36.9%(0~70.6%),个体间变异度(RSD)较大,为81.71%;两药合用前预先降低环孢素剂量的环孢素C_(0)达标率更高,未预先降低环孢素剂量亚组内的2例受者环孢素C_(0)均高于治疗窗上限。结论:allo-HSCT受者合用泊沙康唑后与环孢素发生相互作用,导致环孢素C_(0)和C_(0)/D显著升高,建议临床合用泊沙康唑前根据环孢素浓度测定结果预先降低环孢素剂量。两药合用期间定时监测环孢素C_(0),尤其在两药合用7 d后警惕环孢素浓度过高引起的不良反应,及时调整环孢素剂量,实现个体化用药。

OBJECTIVE To explore the effects of posaconazole on the plasma concentration of cyclosporine in recipients of allogeneic hematopoietic stem cell transplantation(allo-HSCT).METHODS Twenty-seven allo-HSCT recipients were enrolled,who were treated with cyclosporine for immunosuppressive therapy and the plasma concentration was within the therapeutic window(150-300μg·L^(-1)),and then posaconazole was used to prevent fungal infections.The trough concentration(C_(0))and concentration-dose ratio(C_(0)/D)of cyclosporine in the recipients before and 1-10 days after combining use of posaconazole were collected and compared.RESULTS After allo-HSCT recipients were treated combining with posaconazole,the C_(0) of cyclosporine increased significantly.After correction of dose,it was found that C_(0)/D increased most significantly during the combination use of two drugs for 7-10 days(P<0.01).Sixteen cases whose C_(0) of cyclosporine was within the therapeutic window during the study period were analyzed.The daily dose of cyclosporine was decreased from(2.55±0.80)mg·kg^(-1) before the combination to(1.61±0.43)mg·kg^(-1) after the combination with posaconazole,and the decrease rate was 36.9%(0-70.6%)approximately.The inter-individual coefficient of variation(RSD)was 81.71%,which was relatively high.The compliance rate of cyclosporine C_(0) was higher when the cyclosporine dose was reduced before the combination of two drugs.The cyclosporine C_(0) of 2 substandard recipients in the subgroup without reduction of cyclosporine dose was higher than the upper limit of therapeutic window.CONCLUSION Posaconazole interacts with cyclosporine when combined use in allo-HSCT recipients.Posaconazole increases the C_(0) and C_(0)/D of cyclosporine significantly.It is recommended to reduce the cyclosporine dose according to the results of cyclosporine concentration before combining use of posaconazole.It is suggested that cyclosporine C_(0) monitor regularly during the combination use of two drugs,especially after 7 days.The adverse reactions caused by excessive cyclosporine concentration should be paid attention,and the cyclosporine dose should be adjusted in time to achieve individualized medication.