Source: Base de données publique des médicaments (FR) Revision Year: 2011 Publisher: Bayer Vital GmbH, D-51368 Leverkusen Tel.: (02 14) 30 – 51348 Fax: (02 14) 30 – 51603 Email address: bayer-vital@bayerhealthcare.com
Pharmacotherapeutic group: thyroid/antithyroid drugs
ATC code: H03BC
Perchlorate competitively inhibits the thyroid’s iodine uptake mechanism, iodination and affects iodisation by flushing the thyroid of iodide that is accumulating but has not yet been incorporated into a thyroglobulin molecule.
Re-utilisation of iodide released outside the thyroid during deiodination of thyroid hormone is also inhibited.
The uptake of iodide split off on administration of iodinated contrast agents may likewise be competitively inhibited by perchlorate. The same applies to uptake of technetium pertechnetate.
Perchlorate takes effect wherever, as in the thyroid, there is an active iodine transport mechanism (e.g. in the salivary gland) and renal excretion of iodide is also increased.
The antithyroid effect is based on the occurrence of iodine depletion.
Absorption of perchlorate occurs within a matter of minutes. The onset of action in thyroid cells after oral administration is very rapid. After a single dose, the blockade of iodine uptake lasts only a few hours. It is shortened in hyperthyroidism, which means that several doses per day are necessary in order to maintain effective serum concentrations.
When administered as an adjunct to radionuclide scans, the blockade of radionuclide uptake persists even after the subsequent fall in serum perchlorate concentration.
The half-life of perchlorate in humans is not precisely known. Peak tissue levels in the thyroid are attained after 4 hours.
Perchlorate binds to albumin. It is not metabolised in vivo and is excreted rapidly and almost completely unchanged via the renal route; >95% is eliminated after 72 hours.
Oral administration of 1 or 2 g showed no toxic effects in humans.
I.v. injection of 250 mg sodium perchlorate in rabbits had no toxic effects, although intracardiac injection of 500 mg induced transient hind leg paralysis.
Doses of 250 mg/kg body weight for 40 weeks resulted in no toxic adverse effects in animal studies. In mice, toxic phenomena such as signs of paralysis, skeletal changes, exophthalmos, reduced reactions and hair loss have been described dose-dependently at or above a dosage of 1460 mg/kg BW.
No mutagenicity studies are available for sodium perchlorate.
In rats, the extrathyroid tumour rate on discontinuous long-term treatment with high doses of perchlorate was within the range of the spontaneously expected tumour rate.
Polymorphic changes to breast and thyroid are described, although in no instances was the threshold for malignant changes crossed in animal studies.
Insufficient animal studies are available to be able to rule out a possible embryotoxic/fetotoxic effect of sodium perchlorate.
In the rat, oral administration of a 1% potassium perchlorate solution did not interfere with either implantation or survival of the embryo up to day 13 p.c.
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