Skip to main content
SpringerLink
Log in

Repeated KI Prophylaxis in Case of Prolonged Exposure to Iodine Radioisotopes: Pharmacokinetic Studies in Adult Rats

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

To propose a new and effective dose regimen for stable potassium iodide (KI) repeated prophylaxis in case of prolonged exposure to radioactive iodine.

Methods

The pharmacokinetics of iodine was determined in rats by compartmental analyses after intravenous and oral administrations of the optimal dose of 1 mg/kg KI, which was previously selected in a dose-effect study. The thyroid protection against iodine-125 incorporation was followed during 24 h after a single oral dosing of KI. A repeated KI prophylaxis was modeled using initial estimates of iodine pharmacokinetic parameters.

Results

A dose regimen consisting in administrations of 1 mg/kg daily for 8 days was selected and studied. Plasma iodine concentrations predicted by simulation were verified by experimental data and varied after the third dose of KI between 174 and 1190 μg/l. The inhibition study of iodine-125 binding in the thyroid as a function of the time showed that the protection effect of KI could be correlated to stable iodine plasma concentrations. Hence, a theoretical decrease in iodine-125 thyroid uptake from 63 to 88% could be achieved in a 24 h-interval between two KI doses.

Conclusion

Given the satisfactory levels of thyroid protection, this dose regimen could be envisaged in order to extent KI indications for repeated prophylaxis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Mahoney MC, Lawvere S, Falkner KL, Averkin YI, Ostapenko VA, Michalek AM, et al. Thyroid cancer incidence trends in Belarus: examining the impact of Chernobyl. Int J Epidemiol. 2004;33:1025–33.

    Article  Google Scholar 

  2. Shakhtarin VV, Tsyb AF, Stepanenko VF, Orlov MY, Kopecky KJ, Davis S. Iodine deficiency, radiation dose, and the risk of thyroid cancer among children and adolescents in the Bryansk region of Russia following the Chernobyl power station accident. Int J Epidemiol. 2003;32:584–91.

    Article  CAS  Google Scholar 

  3. Verger P, Aurengo A, Geoffroy B, Le Guen B. Iodine kinetics and effectiveness of stable iodine prophylaxis after intake of radioactive iodine: a review. Thyroid. 2001;11:353–60.

    Article  CAS  Google Scholar 

  4. Reiners C, Schneider R. Potassium iodide (KI) to block the thyroid from exposure to I-131: current questions and answers to be discussed. Radiat Environ Biophys. 2013;52:189–93.

    Article  CAS  Google Scholar 

  5. World Health Organization. Iodine thyroid blocking: guidelines for use in planning for and responding to radiological and nuclear emergencies. Geneva; 2017, p. 46.

  6. Saxena KM, Chapman EM, Pryles CV. Minimal dosage of iodide required to suppress uptake of iodine-131 by normal thyroid. Science. 1962;138:431–3.

    Article  Google Scholar 

  7. Cuddihy RG. Thyroidal iodine-131 uptake, turnover and blocking in adults and adolescents. Health Phys. 1966;12:1021–5.

    Article  CAS  Google Scholar 

  8. Kunii Y, Uruno T, Mukasa K, Sekiya K, Iwaku K, Suzuki A, et al. Inhibitory effect of low-dose inorganic iodine on thyroidal radioactive iodine uptake in healthy Japanese adults. Endocr J. 2016;63:21–7.

    Article  CAS  Google Scholar 

  9. Sternthal E, Lipworth L, Stanley B. Suppression of thyroid radioiodine uptake by various doses of stable iodide. N Engl J Med. 1980;303:1083–8.

    Article  CAS  Google Scholar 

  10. Blum M, Eisenbud M. Reduction of thyroid irradiation from 131-I by potassium iodide. J Am Med Assoc. 1967;200:1036–40.

    Article  CAS  Google Scholar 

  11. Phan G, Rebiere F, Suhard D, Legrand A, Carpentier F, Sontag T, et al. Optimal KI prophylactic dose determination for thyroid radiation protection after a single administration in adult rats. Dose-Response. 2017;15:1–8.

    Article  Google Scholar 

  12. Landon G, Bouvier-Capely C, Legrand A, Sontag T, Finance G, Saint-Hilaire M, et al. Validation and comparison of two calibration methods for themeasurement of stable iodine in the urinary matrix by ICP-MS: standard addition vs external calibration. Am J Anal Chem. 2017;8:245–63.

    Article  CAS  Google Scholar 

  13. Gabrielsson J, Meibohm B, Weiner D. Pattern recognition in pharmacokinetic data analysis. AAPS J. 2016;18:47–63.

    Article  CAS  Google Scholar 

  14. Gabrielsson J, Weiner D. Pharmacokinetics and pharmacodynamic data analysis: concepts and applications. Stockholm: Swedish Academy of Pharmaceutical Sciences; 2016.

    Google Scholar 

  15. Akaike H. A new look at the statistical model identification. IEEE Trans Autom Control. 1974;19:716–23.

    Article  Google Scholar 

  16. Gabrielsson J, Weiner D. Akaike and Schwarz criteria. Pharmacokinetics and pharmacodynamic data analysis: concepts and applications. Stockholm: Swedish Academy of Pharmaceutical Sciences; 2016. p. 389.

  17. Schwarz G. Estimating the dimension of a model. Ann Stat. 1978;6:461–4.

    Article  Google Scholar 

  18. Abrahamyan HG, Hovhannisyan AS. Comparative pharmacokinetics of iodide anion at administration of iodine preparations. New Armenian Medical J. 2011;5:26–32.

  19. Berkovski V. New iodine models family for simulation of short-term biokinetics processes, pregnancy and lactation. Food Nutr Bull. 2002;23:87–94.

    Article  Google Scholar 

  20. McLanahan ED, Andersen ME, Fisher JW. A biologically based dose-response model for dietary iodide and the hypothalamic-pituitary-thyroid axis in the adult rat: evaluation of iodide deficiency. Toxicol Sci. 2008;102:241–53.

    Article  CAS  Google Scholar 

  21. Jang M, Kim HK, Choi CW, Kang CS. Age-dependent potassium iodide effect on the thyroid irradiation by 131I and 133I in the nuclear emergency. Radiat Prot Dosim. 2008;130:499–502.

    Article  CAS  Google Scholar 

  22. Jang M, Kim HK, Choi CW, Kang CS. Thyroid dose estimation with potassium iodide (KI) administration in a nuclear emergency. Radiat Prot Dosim. 2008;132:303–7.

    Article  CAS  Google Scholar 

  23. Koutras DA, Pharmakiotis AD, Koliopoulos N, Tsoukalos J, Souvatzoglou A, Sfontouris J. The plasma inorganic iodine and the pituitary-thyroid axis in pregnancy. J Endocrinol Investig. 1978;1:227–31.

    Article  CAS  Google Scholar 

  24. Nagataki S, Shizume K, Nakao K. Effect of iodide on thyroidal iodine turnover in hyperthyroid subjects. J Clin Endocrinol Metab. 1970;30:469–78.

    Article  CAS  Google Scholar 

  25. Liberman CS, Pino SC, Fang SL, Braverman LE, Emerson CH. Circulating iodide concentrations during and after Pregnancy1. J Clin Endocrinol Metab. 1998;83:3545–9.

    CAS  PubMed  Google Scholar 

  26. Paul T, Meyers B, Witorsch RJ, Pino S, Chipkin S, Ingbar SH, et al. The effect of small increases in dietary iodine on thyroid function in euthyroid subjects. Metabolism. 1988;37:121–4.

    Article  CAS  Google Scholar 

  27. Abraham GE. Serum inorganic iodide levels following ingestion of a tablet form of Lugol solution: evidence for an enterohepatic circulation of iodine. The Original Internist. 2004;11:29–34.

    Google Scholar 

  28. Delgado G, Muñoz-Torres C, Orozco-Esquivel T, Anguiano B, Aceves C. Total iodine quantification in fluids and tissues from iodine- or iodide-supplemented rats by ion chromatography following microwave-assisted digestion. Thyroid. 2015;25:352–60.

    Article  CAS  Google Scholar 

  29. Gilbert ME, McLanahan ED, Hedge J, Crofton KM, Fisher JW, Valentin-Blasini L, et al. Marginal iodide deficiency and thyroid function: dose-response analysis for quantitative pharmacokinetic modeling. Toxicology. 2011;283:41–8.

    Article  CAS  Google Scholar 

  30. Shelor CP, Dasgupta PK. Review of analytical methods for the quantification of iodine in complex matrices. Anal Chim Acta. 2011;702:16–36.

    Article  CAS  Google Scholar 

  31. Sun X, Lu L, Shan L, Shan Z, Teng W. Iodine storage and metabolism of mild to moderate iodine-deficient pregnant rats. Thyroid. 2017;27:846–51.

    Article  CAS  Google Scholar 

  32. Leggett RW. A physiological systems model for iodine for use in radiation protection. Radiat Res. 2010;174:496–516.

    Article  CAS  Google Scholar 

  33. McLanahan ED, Campbell JL Jr, Ferguson DC, Harmon B, Hedge JM, Crofton KM, et al. Low-dose effects of ammonium perchlorate on the hypothalamic-pituitary-thyroid axis of adult male rats pretreated with PCB126. Toxicol Sci. 2007;97:308–17.

    Article  CAS  Google Scholar 

  34. Clewell RA, Merrill EA, Yu KO, Mahle DA, Sterner TR, Mattie DR, et al. Predicting fetal perchlorate dose and inhibition of iodide kinetics during gestation: a physiologically-based pharmacokinetic analysis of perchlorate and iodide kinetics in the rat. Toxicol Sci. 2003;73:235–55.

    Article  CAS  Google Scholar 

  35. Leggett R. An age-specific biokinetic model for iodine. J Radiol Prot. 2017;37:864–82.

    Article  Google Scholar 

  36. Ramsden D, Passant FH, Peabody CO, Speight RG. Radioiodine uptakes in the thyroid studies of the blocking and subsequent recovery of the gland following the administration of stable iodine. Health Phys. 1967;13:633–46.

    Article  CAS  Google Scholar 

  37. Braverman ER, Blum K, Loeffke B, Baker R, Kreuk F, Yang SP, et al. Managing terrorism or accidental nuclear errors, preparing for iodine-131 emergencies: a comprehensive review. Int J Environ Res Public Health. 2014;11:4158–200.

  38. Nagataki S, Ingbar SH. Relation between qualitative and quantitative alterations in thyroid hormone synthesis induced by varying doses of iodide. Endocrinology. 1964;74:731–6.

    Article  CAS  Google Scholar 

  39. Lebsir D, Manens L, Grison S, Lestaevel P, Ebrahimian Chiusa T, Suhard D, et al. Effects of repeated potassium iodide administration on genes involved in synthesis and secretion of thyroid hormone in adult male rats. Mol Cell Endocrinol. 2018;474:119–26.

    Article  CAS  Google Scholar 

  40. Zanzonico PB, Becker DV. Effects of time of administration and dietary iodine levels on potassium iodide (KI) blockade of thyroid irradiation by 131I from radioactive fallout. Health Phys. 2000;78:660–7.

    Article  CAS  Google Scholar 

Download references

Acknowledgments and Disclosures

The authors are thankful to the Central Army Pharmacy for providing solutions of KI, Dr. Delphine Denais-Lalieve (DVM), Mélanie Berchet, Amandine Sache, Romain Granger and Frédéric Voyer from the animal experiment support group of IRSN for animal care. These studies were supported by the research program in Nuclear Safety and Radiation Protection of the French National Research Agency (ANR) (contract number ANR-11-RSNR-0019). The authors declared no potential conflicts of interest with respect to research, authorship and publication of this article.

Author information

Authors and Affiliations

  1. Health Division, Institute for Radiation Protection and Nuclear Safety, 31 avenue de la Division Leclerc, F-92260, Fontenay-aux-Roses, France

    Guillaume Phan, Rym Chioukh, David Suhard, Alexandre Legrand, Charlotte Moulin, Thibaud Sontag, François Rebière, Céline Bouvier-Capely, Michelle Agarande, Valérie Renaud-Salis & Jean-René Jourdain

Authors
  1. Guillaume Phan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rym Chioukh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David Suhard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexandre Legrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Charlotte Moulin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thibaud Sontag
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. François Rebière
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Céline Bouvier-Capely
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michelle Agarande
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Valérie Renaud-Salis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jean-René Jourdain
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guillaume Phan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Phan, G., Chioukh, R., Suhard, D. et al. Repeated KI Prophylaxis in Case of Prolonged Exposure to Iodine Radioisotopes: Pharmacokinetic Studies in Adult Rats. Pharm Res 35, 227 (2018). https://doi.org/10.1007/s11095-018-2515-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11095-018-2515-1

Key words

Search

Navigation