Population pharmacokinetics of tacrolimus in pediatric patients with systemic-onset juvenile idiopathic arthritis: Initial dosage recommendations

Pediatric patients with systemic-onset juvenile idiopathic arthritis (SOJIA) may be treated with tacrolimus. However, the therapeutic range for tacrolimus is narrow with considerable inter- and intra-individual variability, making it difficult to formulate an ideal dosage regimen for personalized treatment. The purpose of the present study was to set up a population pharmacokinetics (PPK) model of tacrolimus treatment for SOJIA to determine the optimal initial dosage. Patients with SOJIA were analyzed using non-linear mixed-effects modeling. Different regimens were analyzed using Monte Carlo simulation with concentration profiles. A first-order absorption and elimination one-compartment model was selected as the most appropriate model for SOJIA. Based on initial dosage recommendations, the regimen of 0.5 mg every 24 h (q24h) appeared to be most suitable for subjects with a body weight of 5 kg, while the 0.5 mg q12h regimen was most suitable for subjects with a body weight of 15-25 kg, the 1/0.5 mg q24h regimen was appropriate for the 26-35 kg group and the 1 mg q12h regimen was suitable for the subjects with a body weight of 36-50 kg. To the best of our knowledge, the present study established the first PPK model of tacrolimus treatment that may be used for the selection of the initial dose based on body weight of pediatric patients with SOJIA.