Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: Therapeutic radiopharmaceuticals Iodine (I-131) compounds.
ATC code: V10XA01.
The pharmacological active substance is iodine-131 in the form of sodium iodide that is taken up by the thyroid. It decays mainly there during its long residence time and in this manner induces a 

selective irradiation of this organ. In the small amounts of substance used for diagnostic and thera- peutic procedures no pharmacodynamic effects of sodium iodide (I-131) are to be expected. More than 90% of the radiation effects result from emitted β radiation which has a mean range of 0.5 mm. The β irradiation will dose dependently decrease cell function and cell division leading to cell destruction. The short range and almost absence of uptake of sodium iodide (I-131) outside the thy- roid lead to a negligible amount of irradiation exposure outside the thyroid gland.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
Absorption
After oral administration sodium iodide I-131 is absorbed rapidly from the upper gastrointes- tinal tract (90% in 60 minutes). The absorption is influenced by gastric emptying. It is in- creased by hyperthyroidism and decreased by hypothyroidism.

In studies on the dissolution of sodium iodide I-131 capsules it was shown that the dissolution took place within 5 – 12 minutes and that the radioactivity was homogeneously spread over the gastric mucosa.

Studies on the serum activities levels showed that after a fast increase, - persisting 10 – 20 minutes -, the equilibrium was reached after approximately 40 minutes. After oral administration of a sodium iodide I-131 solution the equilibrium was measured to be at the same time.

Distribution and Organ uptake
The pharmacokinetics follows that of unlabelled iodide. After entering the blood stream it is dis- tributed in the extra thyroidal compartment. From here it is predominantly taken up by the thyroid that extracts approximately 20 % of the iodide in one pass or excreted renally. The uptake of iodide in the thyroid reaches a maximum after 24-48 hours, 50 % of the maximum peak is reached after 5 hours. The uptake is influenced by several factors: the age of the patient, the volume of the thyroid, renal clearance, the level of circulating iodide and by other medicinal products (see section 4.5).
The iodide clearance by the thyroid is usually 5- 50 ml/min. In case of iodine shortage it is however increased to up to 100 ml/min and during hyperthyroidism to up to 1000 ml/min. In case of iodine overload it can be decreased to 2 – 5 ml/min. Iodide accumulates also in the kidneys.
Small amounts of iodide I-131 are taken up by salivary glands, gastric mucosa and would also be localised in breast milk, the placenta and choroid plexus.

The iodide that has been taken up by the thyroid follows the known metabolism of the thyroid hormones and is incorporated in the organic compounds from which the thyroid hormones are syn- thesised.

Half-Life
The effective half-life of radioiodine in plasma is in the order of 12 hours whereas that for radioio- dine taken up by the thyroid gland is about 6 days. Thus after administration of sodium iodide I- 131 approximately 40% of the activity has an effective half-life of 0.4 days and the remaining 60% 8 days.

Elimination
Urinary excretion is 37-75%, faecal excretion is about 10% with almost negligible excretion in sweat.

The urinary excretion is characterised by the renal clearance which constitutes approximately 3 % of the renal flow and is relatively constant from one person to another. It is lower in hypothyroid- ism and in impaired renal function and higher in hyperthyroidism. In euthyroid patients with nor- mal renal function 50 – 75 % of the administered activity is excreted in urine within 48 hours.