Anzeige
Erschienen in:
05.04.2018 | Original Research Article
Infliximab Pharmacokinetics are Influenced by Intravenous Immunoglobulin Administration in Patients with Kawasaki Disease
Erschienen in: Clinical Pharmacokinetics | Ausgabe 12/2018
Einloggen, um Zugang zu erhaltenAbstract
Background
Infliximab, a monoclonal antibody directed against tumor necrosis factor-α, is being evaluated as adjunctive therapy to intravenous immunoglobulin (IVIG) for treatment of young children with acute Kawasaki disease (KD).
Objective
The aim of this study was to develop a population pharmacokinetic (PopPK) model for infliximab in children with KD, and to evaluate the impact of covariates on infliximab disposition. Specifically, we wanted to investigate the effect of body weight and IVIG administration on PK parameters.
Methods
In the current PopPK analysis, 70 subjects with a median (interquartile range) age of 2.9 years (1.3–4.4) were included from two randomized controlled trials. Infliximab concentration–time data were best described by a two-compartment model with first-order elimination using non-linear mixed-effects modeling (NONMEM 7.3).
Results
The clearance, volume of distribution of the central (V1) and peripheral (V2) compartment, and intercompartmental clearance estimates (95% confidence interval) from the PopPK analysis were 0.117 (0.091–0.134) L/day, 0.801 (0.545–0.960) L, 0.962 (0.733–1.759) L, and 0.692 (0.482–1.779) L/day, respectively. Allometric body weight was included on all parameters of the structural model and a covariate analysis revealed that administering infliximab after IVIG, as opposed to before, resulted in a 50% decrease in V2.
Conclusions
Our study shows that the timing of infliximab administration relative to IVIG administration affects the disposition of the monoclonal antibody. These results may have important implications for other monoclonal antibodies administered in combination with IVIG for treating inflammatory diseases.