El-Awady Shaymaa M M, El Afifi Amal M, Afifi Rania, Sabri Nagwa A, Ahmed Marwa Adel
Clinical Pharmacy Department, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt.
Clinical Hematology and Bone Marrow Transplantation Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University Hospitals, Ain Shams University, Cairo, Egypt.
Eur J Drug Metab Pharmacokinet. 2025 Jan;50(1):53-64. doi: 10.1007/s13318-024-00927-y. Epub 2024 Nov 27.
Cyclosporin A (CsA) exhibits a narrow therapeutic index and large inter-individual variation in pharmacokinetics. Two intermittent and 24-h continuous infusions (CI) are both commonly used regimens in hematopoietic stem cell transplantation (HSCT), with no universal consensus. The objective of this study was to assess whether CsA as a 2-h, twice-daily intravenous infusion (2 h/12 h) is non-inferior to 22 h CI every 24 h (22 h-CI/24 h) in terms of acute graft-versus-host disease (aGVHD) incidence and adverse events in allogeneic HSCT adult patients.
An open-label randomized trial recruited 31 allogeneic HSCT patients to receive the 2 h/12 h or 22 h-CI/24 h regimen. The primary outcomes were the incidence of aGVHD and CsA-related adverse events. The secondary outcomes included the correlation between the time concentration and area under the concentration-time curve (AUC) of 2 h/12 h versus 22 h-CI/24 h regimens.
Six (19.4%) patients developed aGVHD. There was no statistically significant difference between the two groups concerning the incidence of aGVHD (13.3% in 2 h/12 h vs. 25% in 22 h-CI/24 h; p = 0.359). The distribution of different aGVHD types (p = 0.20) and mortality (p = 0.9) were not significantly different between the two groups. The two groups did not differ at any time with respect to AUCs, nephrotoxicity, hepatotoxicity, or electrolyte disturbance.
The study suggested that the 2 h/12 h regimen is non-inferior to the conventional regimen (22 h CI/24 h) in terms of aGVHD incidence and adverse events. Further research is necessary to validate these findings and to guide practice, considering the small sample size of this study.
ClinicalTrials.gov identifier NCT04575779 with initial release on 19 September 2020-Retrospectively registered, https://clinicaltrials.gov/study/NCT04575779 .
环孢素A（CsA）治疗指数窄，药代动力学个体差异大。在造血干细胞移植（HSCT）中，两种间歇性给药方案和24小时持续输注（CI）方案都常用，但尚无统一共识。本研究的目的是评估在异基因HSCT成年患者中，环孢素A每日两次静脉输注2小时（2小时/12小时）方案在急性移植物抗宿主病（aGVHD）发生率和不良事件方面是否不劣于每24小时22小时持续输注（22小时-CI/24小时）方案。
一项开放标签随机试验招募了31例异基因HSCT患者，接受2小时/12小时或22小时-CI/24小时方案。主要结局是aGVHD发生率和环孢素A相关不良事件。次要结局包括2小时/12小时与22小时-CI/24小时方案的时间浓度与浓度-时间曲线下面积（AUC）之间的相关性。
6例（19.4%）患者发生aGVHD。两组在aGVHD发生率方面无统计学显著差异（2小时/12小时组为13.3%，22小时-CI/24小时组为25%；p = 0.359）。两组不同类型aGVHD的分布（p = 0.20）和死亡率（p = 0.9）无显著差异。两组在任何时间的AUC、肾毒性、肝毒性或电解质紊乱方面均无差异。
该研究表明，在aGVHD发生率和不良事件方面，2小时/12小时方案不劣于传统方案（22小时CI/24小时）。考虑到本研究样本量小，有必要进一步研究以验证这些发现并指导实践。
ClinicalTrials.gov标识符NCT04575779，于2020年9月19日首次发布——回顾性注册，https://clinicaltrials.gov/study/NCT04575779 。
