Population Pharmacokinetics and Initial Dosage Recommendation of Tacrolimus in Children with Juvenile Dermatomyositis

Background: There is a gap in the pharmacokinetic data on tacrolimus in children with juvenile dermatomyositis (JDM). This study aimed to develop a population pharmacokinetics (PopPK) model for tacrolimus in patients with JDM and formulate model-based recommended dosing regimens. Methods: The PopPK model for tacrolimus was retrospectively developed in 31 children with JDM using nonlinear mixed-effects modeling. The trough concentrations of tacrolimus at different doses were simulated using the Monte Carlo method in children with different body weights. Results: The one-compartment model with first-order absorption and elimination best described the pharmacokinetic data of tacrolimus. In the final model, body weight and concomitant use of voriconazole (VRC) significantly affected the apparent clearance (CL/F) of tacrolimus. The calculation of interindividual clearance was performed as follows: 12.635 × (WT/33.5) 0.296 × (1−0.426 × VRC). The tacrolimus CL/F ratio in children with JDM was 1:0.574 between those without VRC coadministration and those with VRC coadministration at equivalent body weights. For patients with JDM and body weights of 10–20, 20–30, 30–40, and 40–60 kg, the recommended initial doses of tacrolimus without the combined use of VRC were 0.12, 0.08, 0.06, and 0.05 mg·kg −1 ·d −1 (q12h), respectively; the recommended initial doses of tacrolimus with the combined use of VRC were 0.07, 0.05, 0.04, and 0.03 mg·kg −1 ·d −1 (q12h), respectively. Conclusions: This is the first study to establish a PopPK model for tacrolimus. Drug dosage regimens devised on the basis of this model provide evidence-based recommendations for patients with JDM.