ATC Vet Code: QH 03 BB 01
Pharmacotherapeutic group
Systemic hormonal products excl. sex hormones and insulin; thyroid therapy; antithyroid preparations; sulphur-containing imidazole derivatives.
Pharmacodynamic properties
Carbimazole is the prodrug of thiamazole (methimazole). Although carbimazole has inherent antithyroid activity, it is almost totally converted to thiamazole soon after its oral administration in vivo in humans and cats. Thiamazole results in dose-dependent inhibition of the thyroid peroxidase-catalysed reactions involved in thyroid hormone synthesis, including oxidation of iodide and iodination of tyrosyl residues in thyroglobulin, thereby inhibiting neosynthesis of thyroid hormones. Thiamazole also interferes with the coupling of iodotyrosines to iodothyronines via inhibition of thyroid peroxidase or by binding and altering the structure of thyroglobulin, this reaction being more sensitive to inhibition than the formation of iodotyrosines. The inhibitory action of thiamazole is reversible. Thiamazole does not inhibit the action of thyroid hormones already formed and present in the thyroid glands or bloodstream, or interfere with the effectiveness of administered exogenous thyroid hormone (iatrogenic hyperthyroidism). This explains why the length of the latency period until normalisation of serum concentrations of thyroxine and triiodothyronine, and thus to clinical improvement, differs between individuals.
Pharmacokinetic properties
Carbimazole is rapidly absorbed from the gastrointestinal tract after oral administration and hydrolysed in the gastrointestinal tract (or immediately after entering into the circulation) to the active metabolite thiamazole (methimazole). The absolute bioavailability of thiamazole from carbimazole in Vidalta 15 mg tablets is 88%. Following oral administration of one tablet of Vidalta 10 mg to healthy fasted cats, maximum thiamazole concentrations are observed 3-4 hours after administration, with a mean peak concentration of thiamazole of 0.54-0.87 µg/ml. Following oral administration of one tablet of Vidalta 15 mg to healthy fasted cats, maximum thiamazole concentrations are observed 5-7 hours after administration, with a mean peak concentration of thiamazole of 0.72-1.13 µg/ml. For both strengths, the thiamazole concentration/time profile is devoid of pronounced peak and thiamazole persists in the circulation at least 20 and 24 hours for Vidalta 10 mg and Vidalta 15 mg, respectively. The presence of food in the gastrointestinal tract at the time of administration has been shown to increase the bioavailability of thiamazole. When tablets are administered with food, both Cmax and AUClast may be increased whereas tmax is not expected to change. No cumulative effects are observed upon repeated administration.The tissue distribution of mercaptoimidazoles has not been specifically studied in cats but has been fully described in rodents. Thiamazole is mainly concentrated in the thyroid and adrenal glands, and can be found to a lesser extent in the thymus, diaphragm, kidneys, brain, liver, colon, testes, small intestine, stomach and plasma. Mercaptoimidazoles have also been shown to cross the placental barrier. In rats, thiamazole is excreted mainly via the urine, and to a lesser extent in the faeces.