Applicability of the JPKD System for Predicting Tacrolimus Blood Concentrations in Children with Henoch-Schönlein Purpura Nephritis

OBJECTIVE  To investigate the predictive ability of JPKD population pharmacokinetic software for tacrolimus blood concentrations in children with Henoch-Schönlein purpura nephritis(HSPN) and to analyze the influencing factors.

METHODS A retrospective study was conducted on children with HSPN treated with tacrolimus and regularly monitored the trough concentration in the Children's Hospital Affiliated to Kunming Medical University from June 2016 to June 2023. JPKD was used to predict theoretical tacrolimus dose-adjusted blood concentrations, and Pearson analysis was used to analyze the correlation of the results; weighted deviation assessment was used to evaluate the predictive ability of JPKD. Univariate and multivariate Logistic regression analyses were used to screen for factors influencing the predictive accuracy of the JPKD. Receiver operating characteristic(ROC) curve was used to assess the judgmental value of the influencing factors on the predictive accuracy of the software.

RESULTS  A total of 132 therapeutic drug monitoring data points from 43 children with HSPN were included. The measured tacrolimus blood concentration after dose adjustment was 3.94(3.18, 5.43)ng·mL⁻¹, while the JPKD system predicted concentration was 3.78(2.49, 5.66) ng·mL⁻¹. The mean absolute weighted deviation and relative prediction error were 39.03% and 7.64%, respectively. Pearson analysis demonstrated correlation between predicted and measured values, with a prediction accuracy rate of 51.81%. Univariate analysis revealed that age, body weight, height, dosage, aspartate transaminase(AST), serum creatinine, platelet count, and concomitant use of Wuzhi capsules affected JPKD prediction accuracy. Further Logistic regression analysis showed that only AST significantly influenced the prediction accuracy of JPKD. ROC curve analysis indicated that the AST value had an AUC(95% CI) of 0.751(0.644−0.857)(P<0.01) for predicting JPKD accuracy, with a corresponding cutoff value of 26.0 U·L⁻¹.

CONCLUSION  JPKD demonstrates certain predictive capability for tacrolimus blood concentration in HSPN children, but individualized regimens should be formulated in combination with liver function.