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镰状细胞病患者中氰酸钠的生物利用度以及在体内氰酸盐浓度下体外对珠蛋白合成缺乏抑制作用。

Bioavailability of sodium cyanate in patients with sickle cell disease and the lack of inhibition in vitro of globin synthesis at in vivo concentrations of cyanate.

作者信息

Nigen A M, Manning J M, Peterson C M, White J M

出版信息

J Pharmacol Exp Ther. 1975 Nov;195(2):333-9.

PMID:1185602
Abstract

Studies have been made on the bioavailability in blood of sodium cyantate administered orally in gelatin capsules, in gelatin capsules plus antacid, in enteric-coated capsules and in cocoa butter suppositories administered rectally to patients with sickle cell disease. Maximal blood concentrations of cyanate did not exceed 0.4 mM. Sodium cyanate taken orally in gelatin capsules yielded the highest blood concentrations of the drug, but the peak concentrations and curve areas were not necessarily dose-related. The duration of the drug in the circulation was about 210 minutes. Administration of sodium cyanate in the gelatin capsules, taken with an antacid, improved the dose-response relationship within a given patient. Enteric-coated capsules and suppositories were found to show variable and low bioavailability profiles, respectively. Variability in bioavailability between patients with a given dosage form requires further study. Since the concentration of cyanate attainable in vivo does not inhibit synthesis of either the alpha- or beta-chain of hemoglobin in vitro, previous reports on the inhibitory effects of 10 to 100 mM cyanate on globin synthesis in vitro do not appear to be relevant.

摘要

针对患有镰状细胞病的患者,开展了多项研究,涉及口服明胶胶囊氰酸钠、明胶胶囊加抗酸剂、肠溶胶囊以及直肠给药的可可脂栓剂后,氰酸钠在血液中的生物利用度。氰酸盐的最高血药浓度未超过0.4 mM。口服明胶胶囊中的氰酸钠产生的血药浓度最高,但峰值浓度和曲线面积不一定与剂量相关。药物在循环中的持续时间约为210分钟。在明胶胶囊中与抗酸剂一起服用氰酸钠,可改善特定患者体内的剂量反应关系。结果发现,肠溶胶囊和栓剂的生物利用度分别呈现出可变且较低的特征。给定剂型患者之间生物利用度的变异性需要进一步研究。由于体内可达到的氰酸盐浓度在体外不会抑制血红蛋白α链或β链的合成,因此之前关于10至100 mM氰酸盐对体外珠蛋白合成具有抑制作用的报道似乎并不相关。

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