Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: therapeutic radiopharmaceuticals, iodine (131I) compounds, ATC code: V10XA01
The pharmacological active substance is sodium iodide (131I) in the form of sodium iodide that is taken up by the thyroid. The physical decay takes place essentially in the thyroid gland, where sodium iodide (131I) has a long residence time, delivering a selective irradiation to this organ. In the amount used for therapeutic indications, no pharmacodynamic effects of sodium iodide (131I) 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 (131I) outside the thyroid lead to a negligible amount of irradiation exposure outside the thyroid gland.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Absorption
After oral administration, sodium iodide (131I) is absorbed rapidly from the upper gastrointestinal tract (90 % in 60 minutes). The absorption is influenced by gastric emptying. It is increased by hyperthyroidism and decreased by hypothyroidism.
Studies on the serum activities levels showed that after a fast increase, over 10 to 20 minutes, an equilibrium is reached after about 40 minutes. After oral administration of sodium iodide (131I) solution an equilibrium is reached at the same time.

Distribution and organ uptake
The pharmacokinetics follows that of un-labelled iodide. After entering the blood stream it is distributed 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 iodide uptake 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: patient age, thyroid gland volume, renal clearance, plasmatic concentration of iodide and other drugs (see section 4.5). The iodide clearance by the thyroid gland is usually 5-50 mL/min. In case of iodine deficiency the clearance is increased to 100 mL/min and in case of hyperthyroidism can be up to 1,000 mL/min. In case of iodide overload the clearance can decrease to 2-5 ml/min. Iodide also accumulates in the kidneys.

Small amounts of sodium iodide (131I) are taken up by salivary glands, gastric mucosa and they would also be localised in breast milk, the placenta and choroid plexus.

The iodide fixed by the thyroid enters the known metabolic path of thyroid hormones and is incorporated in the organic substances entering in the synthesis of thyroid hormones.
Biotransformation
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 synthesised.
Elimination
Urinary excretion is 37-75%, faecal excretion is about 10%, with almost negligible excretion in sweat.
Urinary excretion is characterised by the renal clearance, which constitutes about 3% of the renal flow and is relatively constant from one person to another. The clearance is lower in hypothyroidism and in impaired renal function and higher in hyperthyroidism. In euthyroidic patients with normal renal function 50-75% of the administered activity is excreted in urine within 48 hours.
Half-life
The effective half-life of radioiodine in plasma is about 12 hours in blood plasma and about 6 days in the thyroid gland. Thus, after administration of sodium iodide (131I), about 40% of the activity has an effective half-life of 6 hours and the remaining 60% of 8 days.

Renal impairment
Patients with renal impairment may have a decrease in the radioiodine clearance, resulting in increased radiation exposure of sodium iodide (131I) administered. One study showed, for example, that patients with impaired renal function undergoing continuous ambulatory peritoneal dialysis (CAPD) have a clearance of radioiodine 5 times lower than patients with normal kidney function.