Model-Informed Precision Dosing of Tacrolimus Initial Dosage Optimization in Membranous Nephropathy Patients

Abstract

Objective Due to the therapeutic window of tacrolimus is narrow and there are significant individual differences in metabolism, a uniform dosage is prone to result in poor efficacy or increased toxic side effects. This study aimed to explore tacrolimus initial dosage optimization in membranous nephropathy (MN) patients based on model-informed precision dosing (MIPD). Methods Population pharmacokinetic model, an effective tool of MIPD, was constructed using the non-linear mixed effect modeling approach implemented in NONMEM software, which encompassed a range of patient-related data, including demographic characteristics, physiological and biochemical test results, as well as details regarding concurrent medications. Results From the aspect of individualized drug administration, in adult MN patients, the initial dosages of tacrolimus were 0.06 mg/kg, 0.04 mg/kg for patients weighted 50–53 kg, 53–100 kg, respectively. In pediatric MN patients, the initial dosages of tacrolimus were 0.12 mg/kg, 0.10 mg/kg, 0.08 mg/kg, 0.06 mg/kg for patients weighted 10–12.7 kg, 12.7–16.4 kg, 16.4–26.7 kg, 26.7–40 kg, respectively. Conclusion This study was the first time to simultaneously recommend the optimal initial dosage of tacrolimus for both adult and pediatric MN patients based on MIPD. Moreover, the dosage required for pediatric MN patients was higher than that for adult MN patients.