Investigation of factors influencing radioiodine (I-131) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach

Abstract

Radioiodine (I-131) therapy is the common treatment option for benign thyroid diseases. The objective of this study was to characterize I-131 biokinetics in patients with benign thyroid disease and to investigate and quantify the influence of patients' demographic and clinical characteristics on intra-thyroidal I-131 kinetics by developing a population model. Population pharmacokinetic analysis was performed using a nonlinear mixed effects approach. Data sets of 345 adult patients with benign thyroid disease, retrospectively collected from patients' medical records, were evaluated in the analysis. The two-compartment model of I-131 biokinetics representing the blood compartment and thyroid gland was used as the structural model. Results of the study indicate that the rate constant of the uptake of I-131 into the thyroid (k (tu)) is significantly influenced by clinical diagnosis, age, functional thyroid volume, free thyroxine in plasma (fT(4)), use of anti-thyroid drugs, and time of discontinuation of therapy before administration of the radioiodine (THDT), while the effective half-life of I-131 is affected by the age of the patients. Inclusion of the covariates in the base model resulted in a decrease of the between subject variability for k (tu) from 91 (3.9) to 53.9 (4.5)%. This is the first population model that accounts for the influence of fT(4) and THDT on radioiodine kinetics. The model could be used for further investigations into the correlation between thyroidal exposure to I-131 and the outcome of radioiodine therapy of benign thyroid disease as well as the development of dosing recommendations.