2017 - Budapest - Hungary

PAGE 2017: Drug/Disease modelling - Other topics
Valentina Topic Vucenovic

Nonlinear mixed effects modelling approach for investigation of 131I kinetics in patients with benign thyroid disease

Valentina Topic Vucenovic (1), Katarina Vucicevic (1), Zvezdana Rajkovaca (2), Dragi Stanimirovic (2), Goran Vuleta (2), Dijana Jelic (3), Branislava Miljkovic (1)

(1) Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Serbia, (2) Institute of Nuclear Medicine and Thyroid Gland Disease, University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina, (3) Faculty of Medicine, University of Banja Luka, Bosnia and Herzegovina

Objectives: Radioiodine therapy is a common approach in the treatment of benign thyroid diseases. The aim of the study was to investigate factors that influence intrathyroidal kinetics of 131I in patients with benign thyroid disease and to develop population kinetic model using routine clinical data on radioiodine uptake measurement following administration of the tracer activity.

Methods: Demographic and clinical characteristics of patients with benign thyroid disease were retrospectively collected from patients' medical records. Uptake of radioiodine in thyroid (RIU(t)) was measured 4, 24, 48 h, and in some patients 168 h following oral administration of a capsule with nominal test activity of 1.85 MBq of 131I. Population analysis was performed using NONMEM® software (v7.3) and PsN® (v4.6.0). Following covariates were tested: gender, age, diagnosis, functional thyroid volume, presence of cardiovascular disease, thyroid-stimulating hormone (TSH), free thyroxine (fT4), previous therapy with anti-thyroid drugs (ATDs) and therapy discontinuation time before administration of the test activity.

Results: In total 366 adult patients, and 899 uptake measurements were included in the analysis.  The two-compartment model of 131I biokinetics was used as the structural model [1]. The interindividual variability (IIV) of the rate constant of the uptake of radioiodine in the thyroid (ktu) was described by an exponential model, while the residual error was best described by a proportional model. Results of the study indicate that ktu in patients with benign thyroid disease is significantly influenced by diagnosis, age, functional thyroid volume, fT4 in plasma, use of ATDs and time of discontinuation of therapy. According to the final model, effective half-life of 131I in typical patient is 6.56 days, and for each additional year it increases on average by 3.95%. Inclusion of the covariates in the base model resulted in decrease of the IIV for  ktu from 89.8% (7.6%) to 55.6% (4.5%) with shrinkage of 3.9%. Acceptable performances of the final model were confirmed by nonparametric bootstrap analysis and predictive checks.

Conclusion: The developed population kinetic model of 131I explained significant portion of interindividual variability in 131I intrathyroidal kinetics and can be used for estimation of individual time-integrated activity coefficient of 131I needed for patient specific calculation of therapeutic activity for radioiodine therapy of benign thyroid diseases.

[1] Hanscheid H, Lassmann M, Reiners C. Dosimetry prior to I-131-therapy of benign thyroid disease. Zeitschrift fur medizinische Physik (2011) 21:250-7.

Reference: PAGE 26 (2017) Abstr 7151 [www.page-meeting.org/?abstract=7151]
Poster: Drug/Disease modelling - Other topics