关键词: 西罗莫司, CYP3A5, ABCB1, 药物基因组, 治疗药物监测

Abstract: Background：Sirolimus (SRL) is used in children for organ transplantation, autoimmune diseases, lymphatic malformation, vascular malformation, tuberous sclerosis and other diseases. However, it has great pharmacokinetic variability, which requires therapeutic drug monitoring (TDM). Objective：To reveal the causes of abnormal serum concentration of sirolimus. Design：Case report. Methods：We described the clinical data of 2 children with immunodeficiency treated with SRL for 6 months, analyzed the causes of abnormal drug concentration in children, and reviewed the literature. Main outcome measures：Whole blood trough concentration (Cmin) reached the target range of 510 ng·mL-1. Results：For child A, the drug interaction between SRL and voriconazole and CYP3A5 rs776746C/C genotype were the reasons for the slow drug metabolism and abnormal increase of Cmin. The dose decreased to 20% of the initial dose and gradually returned to the standard range. For child B, CYP3A5 rs776746 C/C genotype and ABCB1 gene rs1045642 T /T genotype were the reasons for the decrease of drug clearance rate and the abnormal increase of Cmin. After reducing the initial dose to 50%, the serum concentration of SRL gradually decreased to normal, and the treatment concentration was within the standard range. Conclusion：Systematic method will help to determine the cause of Cmin abnormal value of SRL. The sample factors, clinical factors and genetic factors should be considered before adjusting the treatment plan, and the comprehensive treatment management (CMM) of SRL should be optimized.

Key words: Sirolimus, CYP3A5, ABCB1, Drug gene testing, Therapeutic drug monitoring