Population Pharmacokinetic Approach to the Use of Low Dose Cyclosporine in Patients with Connective Tissue Diseases

An artificial neural network−pharmacokinetic model and its interpretation using Shapley additive explanations

“…The most influential factors on CL output were AGE and WT from the evaluation using Kernel SHAP. These factors were incorporated into the PopPK model as the significant covariates of CL, so that the results from this study were consistent with those of the previous study 24 . Figure 5 suggests that the output CL values decreased with increasing AGE and increased with increasing WT.…”

“…These factors were incorporated into the PopPK model as the significant covariates of CL, so that the results from this study were consistent with those of the previous study. 24 Figure 5 suggests that the output CL values decreased with increasing AGE and increased with increasing WT. It has been reported that the elimination of cyclosporine from blood is age‐dependent and the CL is large in younger patients.…”

“…A previous population PK (PopPK) model of cyclosporin A was used as the comparison model. 24 The same data as the previous study were used for the present analysis, and the data used were from 36 patients with 89 drug blood concentrations. Details of the comparison PopPK model are shown in Table S1 .…”

“…This study was conducted with the approval of the ethics committee of Nihon University (School of Pharmacy, approval number: 20‐012). A previous population PK (PopPK) model of cyclosporin A was used as the comparison model 24 . The same data as the previous study were used for the present analysis, and the data used were from 36 patients with 89 drug blood concentrations.…”