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

Eur J Clin Pharmacol. 2018 Aug;74(8):1037-1045. doi: 10.1007/s00228-018-2459-8. Epub 2018 May 13.

Abstract

Purpose: Radioiodine (131I) therapy is the common treatment option for benign thyroid diseases. The objective of this study was to characterize 131I biokinetics in patients with benign thyroid disease and to investigate and quantify the influence of patients' demographic and clinical characteristics on intra-thyroidal 131I kinetics by developing a population model.

Methods: 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 131I biokinetics representing the blood compartment and thyroid gland was used as the structural model.

Results: Results of the study indicate that the rate constant of the uptake of 131I into the thyroid (ktu) is significantly influenced by clinical diagnosis, age, functional thyroid volume, free thyroxine in plasma (fT4), use of anti-thyroid drugs, and time of discontinuation of therapy before administration of the radioiodine (THDT), while the effective half-life of 131I 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 ktu from 91 (3.9) to 53.9 (4.5)%.

Conclusions: This is the first population model that accounts for the influence of fT4 and THDT on radioiodine kinetics. The model could be used for further investigations into the correlation between thyroidal exposure to 131I and the outcome of radioiodine therapy of benign thyroid disease as well as the development of dosing recommendations.

Keywords: Benign thyroid disorders; Population model; Radioiodine uptake; Variability.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Iodine Radioisotopes / administration & dosage
  • Iodine Radioisotopes / pharmacokinetics*
  • Male
  • Middle Aged
  • Models, Biological
  • Nonlinear Dynamics
  • Retrospective Studies
  • Thyroid Diseases / metabolism*
  • Thyroid Diseases / radiotherapy*
  • Thyroid Gland / radiation effects
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / radiotherapy*
  • Thyroxine / blood
  • Young Adult

Substances

  • Iodine Radioisotopes
  • Thyroxine