异基因造血干细胞移植患者环孢素静脉滴注转换为口服给药的影响因素分析

Influencing Factors Analysis of the Conversion of Cyclosporine from Intravenous Infusion to Oral Administration in Patients with Allogeneic Hematopoietic Stem Cell Transplantation

目的探讨异基因造血干细胞移植(HSCT)患者环孢素(CsA)由静脉滴注转换为口服给药时给药剂量的转换比例,并分析影响转换比例的因素,为临床合理用药提供参考。方法回顾性收集HSCT术后使用CsA的患者病历资料,包括性别、年龄、体质量、相应的生化指标、联合用药、移植物抗宿主病(GVHD)及药品不良反应等。记录并比较CsA由静脉滴注转换为口服给药前最后一次血药浓度/日剂量比(C0/Div)和切换后3~5 d的血药浓度/日剂量比(C0/Dpo),生物利用度的计算采用口服血药浓度/日剂量比除以静脉血药浓度/日剂量比[(C0/Dpo)/(C0/Div)]。采用SPSS软件分析(C0/Dpo)/(C0/Div)和各因素之间的相关性。结果共纳入HSCT患者57例,静脉给药CsA的C0/Div中位数显著大于口服给药的(C0/Dpo)[3.15(1.08~4.89)和0.88(0.14~2.32),P<0.05];(C0/Dpo)/(C0/Div)中位数为0.3(0.11~0.63),静脉滴注转换为口服时给药剂量比例为1:3,其中合并使用伊曲康唑可以显著增加CsA的(C0/Dpo)/(C0/Div),合并使用伊曲康唑,静脉滴注转换为口服时给药剂量的比例为1:2.5。(C0/Dpo)/(C0/Div)与发生GVHD及不良反应的概率有相关性,(C0/Dpo)/(C0/Div)<0.23患者更易发生GVHD(P<0.05),而(C0/Dpo)/(C0/Div)≥0.36患者更易发生不良反应(P<0.05)。结论HSCT患者CsA静脉滴注转换为口服给药时给药剂量比例为1:3,合并使用伊曲康唑时转换比例为1:2.5。在转换给药方式时,应注意监测CsA血药浓度,以保证血药浓度在治疗范围内,从而提高CsA治疗有效性。

Objective To explore the dose conversion ratio of cyclosporine(CsA)from intravenous infusion to oral administration in patients with allogeneic hematopoietic stem cell transplantation(HSCT),and to analyze variable factors affecting the dose conversion ratio so as to provide references for clinical rational drug use.Methods The clinical medical records of patients using CsA after HSCT were collected retrospectively,including gender,age,bodyweight,corresponding biochemical indexes,drug combination,graft versus host disease(GVHD),and adverse drug reactions.The last plasma concentration/daily dose ratio(C0/Div)of CsA before the switch from intravenous infusion to oral administration was recorded,and compared with the plasma concentration/daily dose ratio(C0/Dpo)in 3-5 days after the switch.Bioavailability was calculated by dividing the dose-corrected CsA concentration in oral administration by the dose-corrected CsA concentration in intravenous administration[(C0/Dpo)/(C0/Div)].The SPSS software was used to analyze the correlation between(C0/Dpo)/(C0/Div)and various factors.Results A total of 57 HSCT recipients were included in the study for analysis.The median value of C0/Div in intravenous administration was significantly higher than that of C0/Dpo in oral administration[3.15(1.08-4.89)vs 0.88(0.14-2.32),P<0.05].The median(C0/Dpo)/(C0/Div)value was 0.3(0.11-0.63).The ratio of dosages in the switch from intravenous to oral administration was 1:3,in which the combined itraconazole could significantly increase the(C0/Dpo)/(C0/Div)of CsA.A lower conversion ratio of 1:2.5 was applied in patients taking oral itraconazole.(C0/Dpo)/(C0/Div)was co-related to the GVHD and adverse drug reactions.The patients whose(C0/Dpo)/(C0/Div)values were less than 0.23 were more likely to get GVHD(P<0.05),and patients whose(C0/Dpo)/(C0/Div)values were more than 0.36 were more likely to have adverse drug reactions(P<0.05).Conclusion In HSCT patients,the dose conversion from intravenous infusion to oral administration at a ratio of 1:3 appeared to be appropriate.In patients combined with oral itraconazole,a lower conversion ratio of 1:2.5 was suitable.In order to ensure the concentration within the therapeutic window to improve the effectiveness of CsA treatment,CsA concentration should be monitored when switching the route of administration.