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

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(150～300 μg·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(C0)、浓度剂量比(C...

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

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 (150-300 μg·L^-1), and then posaconazole was used to prevent fungal infections. The trough concentration (C₀) and concentration-dose ratio (C₀/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 C₀ of cyclosporine increased significantly. After correction of dose, it was found that C₀/D increased most significantly during the combination use of two drugs for 7-10 days (P＜0.01). Sixteen cases whose C₀ 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 C₀ was higher when the cyclosporine dose was reduced before the combination of two drugs. The cyclosporine C₀ 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 C₀ and C₀/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 C₀ 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.