Crawley F E, Hyacinthe R, Poitou P, Donath A
Eur J Drug Metab Pharmacokinet. 1983 Jul-Sep;8(3):287-96. doi: 10.1007/BF03188759.
The pharmacokinetics, metabolism and elimination of Itanoxone was studied after a single oral administration of the carbon-14-labelled drug (500 mg) in four male volunteers. The drug was absorbed fairly rapidly with a mean peak plasma level of 10.3 +/- 1.3 micrograms/ml between 3 and 4 hours after dosing. The pharmacokinetics can be described by a two-compartment open model with the central compartment consisting of the extracellular fluid. The mean elimination half-life was 19.4 +/- 8.5 hours. Two metabolites as well as unchanged Itanoxone were detected in plasma. Approximately 37% of the radioactivity was excreted over a five-day period in the urine and 50% in the faeces. There were only traces of free metabolites in the urine as the rest of the radioactive metabolites were associated with glucuronide conjugates. These conjugates consisted of Itanoxone and up to six metabolites. Five of these metabolites have been tentatively identified by comparison of their chromatographic properties by TLC and HPLC with a number of reference compounds. After repeated administration of Itanoxone (250 mg b.i.d.) the maximum level at steady state was about 7 micrograms/ml and the minimum level, 0.6 micrograms/ml. The mean area under the plasma level time curve was 35% higher than in the single dose study after correction for dose.
在4名男性志愿者单次口服500毫克碳 - 14标记的伊他诺酮后，对其药代动力学、代谢及消除情况进行了研究。给药后3至4小时，药物吸收相当迅速，平均血浆峰值水平为10.3±1.3微克/毫升。药代动力学可用二室开放模型描述，中央室由细胞外液组成。平均消除半衰期为19.4±8.5小时。在血浆中检测到两种代谢物以及未变化的伊他诺酮。在五天时间内，约37%的放射性通过尿液排出，50%通过粪便排出。尿液中仅有痕量的游离代谢物，其余放射性代谢物与葡糖醛酸结合物相关。这些结合物由伊他诺酮和多达六种代谢物组成。通过薄层层析（TLC）和高效液相色谱（HPLC）将其中五种代谢物的色谱性质与多种参考化合物进行比较，初步鉴定出了这五种代谢物。多次给予伊他诺酮（250毫克，每日两次）后，稳态时的最高水平约为7微克/毫升，最低水平为0.6微克/毫升。经剂量校正后，血浆水平时间曲线下的平均面积比单剂量研究高35%。
