霉酚酸药时曲线下面积与异基因造血干细胞移植患者腹泻相关性的临床研究OA

Objective To investigate the correlation between mycophenolic acid(MPA)trough concentrations and the area under the concentration-time curve(MPA-AUC)with early post-transplant diarrhea in adult patients diagnosed with malignant hematologic diseases and undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods Adult patients diagnosed with hematologic diseases and treated with allo-HSCT were enrolled.Participants received oral mycophenolate mofetil(MMF)capsule at a daily dose of 0.75-1.50 g,and blood drug concentrations were monitored on day 8 of medication.MPA blood concentration data from 22 patients collected at multiple time points were used to establish a limited sampling model for calculating MPA-AUC0-12h through stepwise forward linear regression analysis.MPA blood concentration data from 27 patients were used for model validation.After model development,an additional 44 patients diagnosed with hematologic malignancies and undergoing allo-HSCT with myeloablative conditioning regimens were included.Based on the occurrence of diarrhea within 30 days post-transplant,patients were divided into diarrhea and non-diarrhea groups,and significant differences in MPA trough concentrations and MPA-AUC0-12h between the two groups were analyzed.Results The established limited sampling model was MPA-AUC0-12h=5.22 × C0+0.46 × C0.5+0.66 × C1.0+3.22 × C4.0+5.22(r2=0.87).Among the 44 patients,the incidence of diarrhea within 30 days post-transplant was 54.54％.MPA-AUC0-12 h values were(18.29±0.89)and(13.36±0.80)mg·h·L-1 in the diarrhea and non-diarrhea groups,respectively,with the diarrhea group significantly higher than the non-diarrhea group(P＜0.05).Receiver operating characteristic curve analysis suggested that MPA-AUC0-12h＞17.25 mg·h·L-1 may increase the risk of early post-transplant diarrhea.MPA trough concentrations were(0.38±0.08)and(0.24±0.03)mg·L-1 in the diarrhea and non-diarrhea groups,respectively,with no statistically significant difference(P＞0.05).Conclusion MPA-AUC0-12 h is closely associated with diarrhea occurring within 30 days post-allo-HSCT.