Population Pharmacokinetics Of Cyclosprin A In Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Objective:(1) To analyse factors which may affect cyclosporine A(Cs A) concentration in whole blood of allogeneic hematopoietic stem cell transplantation(allo-HSCT) patients, and investigate the clinical significance of therapeutic drug monitoring to ensure the rational use of drugs in patients.(2)The purpose of this paper was to establish population pharmacokinetics model of Cyclosprin A in allo-HSCT patients by NONMEM. To evaluate intra-individual and inter-individual variable, and explore CL and Vd influenced by physiological, pathological factors and combination therapy. And to provide refence for individualized medication in clinical practice. The final model was validated by Boostrap method.Methods:(1)79 cases of allo-HSCT patients clinical data after using cyclosporine were Collected, then statistical analyse of the relationship among Cs A plasma concentration and clinical manifestations, biochemical parameters.(2) 1436 copies of plasma concentrations of Cs A were collected from 130 allo-HSCT patients retrospectively. PPK model was set up by NONMEM. The influences factors such as gender, age, weight, postoperative day, blood indicators, renal function and drug combination on paramacokinetic parameters were inwestigated.Results:(1) The average determination results of 553 cases Cs A plasma concentration in 79 patients was 307.51±169.11 ng·ml-1, 447 of 553 cases(80.8%) plasma concentration was a range from 150ng·ml-1 to 600ng·ml-1, 67 cases(12.1%) plasma concentration was less than 150ng·ml-1, 39 cases(7.1%) plasma concentration was higher than 600ng·ml-1. Preliminary analysis results showed that there was a strong correlation among the Cs A concentration,indirect bilirubin and serum magnesium. While the correlation with other biochemical indexes was not obvious.(2)The final model was: CL=11.0*(1+0.0579*(AGE-9.0))*(1+0.206*PPI)*EXP(ETA(1));V=52.4*(1+0.0140*(WT-32))*EXP(ETA(2)). The results were validated to be effective and stable.Conclusion:(1) Cs A plasma concentration was influenced by many factors. There was important clinical significance in monitoring the concentration of Cs A in allo-HSCT patients.(2) The PPK final model of Cs A in allo-HSCT recipients could be established using the NONMEM,the model was stable and reliable,and it could be used as a guide for individual drug delivery based on the clinical drug treatment.