Drug-Drug Interaction and Initial Dosage Optimization of Tacrolimus in Pediatric Nephrotic Syndrome Patients Based on Real-World Data and Model-Informed Precision Dosing.

OBJECTIVE

Tacrolimus is a calcineurin inhibitor and holds an important position in the treatment of Pediatric Nephrotic Syndrome (PNS). However, the pharmacokinetics of tacrolimus are influenced by multiple factors, especially when combined with other medications. This study aims to explore Drug-Drug Interaction (DDI) and initial dosage optimization of tacrolimus in PNS based on real-world data and Model-Informed Precision Dosing (MIPD).

METHODS

The PNS patient data included demographic, clinical laboratory, and combined drug data. Population Pharmacokinetics (PPK) to study DDI and to optimize the initial dosage of tacrolimus in PNS patients was used.

RESULTS

In the final tacrolimus PPK model of PNS patients, wuzhi capsule affected tacrolimus, and when PNS patients took wuzhi capsule at the same time, the clearance rate of tacrolimus decreased by 43%. Furthermore, the initial dosage regimen of tacrolimus for PNS was recommended. When PNS patients were not taking wuzhi capsules, the recommended tacrolimus dosages for 10 kg-23 kg and 23 kg-60 kg pediatric patients were 0.12 mg/kg and 0.10 mg/kg, respectively. When PNS patients were taking wuzhi capsules, the recommended dosage of tacrolimus for 10 kg-60 kg pediatric patients was 0.08 mg/kg.

DISCUSSION: This study explored DDI and initial dosage optimization of tacrolimus in PNS patients based on real-world data and MIPD, and wuzhi capsule with tacrolimus had DDI.

CONCLUSION

The present study recommended an initial tacrolimus dosage regimen for PNS based on the wuzhi capsule.