European Journal of Clinical Pharmacology

, Volume 74, Issue 8, pp 1037–1045 | Cite as

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

  • Valentina Topić Vučenović
  • Zvezdana Rajkovača
  • Dijana Jelić
  • Dragi Stanimirović
  • Goran Vuleta
  • Branislava Miljković
  • Katarina Vučićević
Pharmacokinetics and Disposition



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.


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 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)%.


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.


Radioiodine uptake Variability Population model Benign thyroid disorders 


Author contributions

V.T.V. gathered data, performed analysis, interpreted the results, and wrote the manuscript; Z.R., G.V., and D.S. designed the study and interpreted results; D.J. designed the study and revised the manuscript; B.M. supervised the study and revised the manuscript; K.V. performed the analysis and wrote the manuscript.

Compliance with ethical standards

The study protocol was approved by the Ethics Committee of the University Clinical Centre of the Republic of Srpska and all procedures were in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For the retrospective type of study, formal consent is not required.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

228_2018_2459_MOESM1_ESM.docx (488 kb)
ESM 1 (DOCX 487 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmacy, Faculty of MedicineUniversity of Banja LukaBanja LukaBosnia and Herzegovina
  2. 2.Institute of Nuclear Medicine and Thyroid Gland DiseaseUniversity Clinical Centre of the Republic of SrpskaBanja LukaBosnia and Herzegovina
  3. 3.Department of Pharmacokinetics and Clinical PharmacyUniversity of Belgrade - Faculty of PharmacyBelgradeSerbia

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