首页|Population exposure-response model of 131I in patients with benign thyroid disease

Population exposure-response model of 131I in patients with benign thyroid disease

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  • NSTL
  • Elsevier
Purpose: The study aimed to explore the relationship of different exposure measures with 131I therapy response in patients with benign thyroid disease, estimate the variability in the response, investigate possible covariates, and discuss dosing implications of the results. Methods: A population exposure-response analysis was performed using nonlinear mixed-effects modelling. Data from 95 adult patients with benign thyroid disease were analysed. Evaluated exposure parameters were: administered radioactivity dose (Aa) [MBq], total absorbed dose (ABD) [Gy], maximum of absorbed dose-rate (MXR) [Gy/h] and biologically effective dose (BED) [Gy]. The response was modelled as ordered categorical data: hyper-, eu- and hypothyroidism. The final model performance was evaluated by a visual predictive check. Results: The probability of the outcome following 131I therapy was best described by a proportional-odds model, including the log-linear model of 131I effect and the exponential model of the response-time relationship. All exposure measures were statistically significant with p<0.001, with BED and ABD being statistically better than the other two. Nevertheless, as BED resulted in the lowest AIC value, it was included in the final model. Accordingly, BED value of 289.7 Gy is associated with 80% probability of successful treatment outcome 12 months after 131I application in patients with median thyroid volume (32.28 mL). The target thyroid volume was a statistically significant covariate. The visual predictive check of the final model showed good model performance. Conclusion: Our results imply that BED formalism could aid in therapy individualisation. The larger thyroid volume is associated with a lower probability of a successful outcome.

Radioiodine therapyOutcome probabilityBiologically effective doseBenign thyroid disordersProportional odds modelDose-rate effects

Miljkovic, Branislava、Vucicevic, Katarina、Vucenovic, Valentina Topic、Rajkovaca, Zvezdana、Jelic, Dijana、Stanimirovic, Dragi、Mikov, Momir

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Univ Belgrade, Dept Phammcokinet & Clin Pharm, Fac Pharm, Vojvode Stepe 450, Belgrade 11221, Serbia

Univ Banja Luka, Fac Med, Dept Pharm, Save Mrkalja 14, Banja Luka 78000, Bosnia & Herceg

Univ Clin Ctr Republ Srpska, Inst Nucl Med & Thyroid Gland Dis, 12 Beba Bb, Banja Luka 78000

Univ Banja Luka, Fac Nat Sci & Math, Chem Dept, Mladena Stojanovica 2, Banja Luka 78000, Bosnia &

Univ Novi Sad, Dept Pharmacol Toxicol & Clin Pharmacol, Fac Med, Hajduk Veljkova 3, Novi Sad 21000

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2021

10.1016/j.ejps.2021.105942

European journal of pharmaceutical sciences

European journal of pharmaceutical sciences

ISTP
ISSN：0928-0987
年,卷(期)：2021.165
  • 48