The metabolism of 35S-antithyroid drugs
Başlık:
The metabolism of 35S-antithyroid drugs
Yazar:
Marchant, Brian, author.
ISBN:
9780438057593
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (295 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Advisors: G. M. Wilson.
Özet:
Although antithyroid drugs have been used in the treatment of thyrotoxicosis for 25 years there is virtually no information about the fate of the drugs in current clinical use. Since no chemical methods were available, the metabolism of 35S-labelled antithyroid drugs has been studied in rats and man. Carbimazole was found to be rapidly hydrolysed to methimazole in vitro and in vivo and thus the metabolic fate of methimazole and propylthiouracil has been examined. The tissue distribution and metabolism of single intraperitoneal doses of propylthiouracil and methimazole were studied and the radioactivity analysed by liquid scintillation counting and thin-layer chromatography. Both propylthiouracil and methimazole were selectively accumulated in the thyroid gland and were oxidised by the gland mainly to sulphate. In order to relate the thyroidal drug level with the action of the drug in blocking thyroid hormone synthesis a double isotope method was devised. This enabled the thyroidal metabolism of methimazole and propylthiouracil and the effect on the organification of iodine in the thyroid to be studied simultaneously in the same animal. These experiments showed that propylthiouracil accumulated in the rat thyroid to a greater extent than an equimolar dose of methimazole and had a longer duration of action in inhibiting thyroid hormone synthesis. These findings are consistent with the greater potency of propylthiouracil compared to methimazole in the rat which has been reported in the literature. These studies also suggested that the drugs were directly responsible for the antithyroid effect and not through metabolism to an active metabolite. (Abstract shortened by ProQuest.).
Notlar:
School code: 0547
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(684618.1) | 684618-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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