Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of 14C-propofol.
Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of 14C-propofol.
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男性志愿者亚麻醉静脉注射 14C-异丙酚水包油乳剂的处置。
DOI：
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发表时间：
1988
期刊：
影响因子：
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通讯作者：
M. Rowland
中科院分区：
文献类型：
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作者：
P. Simons;I. Cockshott;E. J. Douglas;E. Gordon;K. Hopkins;M. Rowland
1. 6名男性志愿者静脉注射0.47 mg/kg的14 C-丙泊酚后，5天内尿液中的14 C-丙泊酚清除率为88%，粪便中的14 C-丙泊酚清除率低于2%。2.剂量通过代谢清除，以原型药物排泄的剂量低于0.3%。主要代谢产物为丙泊酚的葡萄糖醛酸结合物及其羟基化衍生物2，6-二异丙基-1，4-喹啉的葡萄糖醛酸和硫酸盐结合物。丙泊酚葡萄糖醛酸苷约占尿液放射性的53%，是给药后30分钟血浆中的主要代谢产物。3.丙泊酚的血药浓度以双相方式从注射后2分钟的最大平均值0.44 μ g/ml下降。第一和第二指数相的半衰期，平均值分别为5分钟和97分钟，受试者之间差异很大。一部分剂量被缓慢清除，可能是由于从灌注较差的组织中缓慢释放。丙泊酚在给药后2 min占血液总放射性的94%，但在给药后3 - 8 h仅占约6%。4.丙泊酚的分布容积约为体重的3 - 4倍，平均全身清除率为2.2 l/min。
1. An intravenous dose of 14C-propofol (0.47 mg/kg) administered to six male volunteers was rapidly eliminated with 88% recovered in the urine in 5 days and less than 2% in faeces. 2. The dose was cleared by metabolism with less than 0.3% excreted unchanged. The major metabolites were the glucuronic acid conjugate of propofol and the glucuronic acid and sulphate conjugates of its hydroxylated derivative, 2,6-diisopropyl-1,4-quinol. Propofol glucuronide accounted for about 53% of the urinary radioactivity and was the major metabolite in plasma from 30 min post dose. 3. The blood concentration of propofol declined in a biphasic manner from a maximum mean value of 0.44 microgram/ml, 2 min after injection. The half-lives of the first and second exponential phases, mean values 5 min and 97 min respectively, varied widely among subjects. A proportion of the dose was cleared slowly, probably due to slow release from less well perfused tissues. Propofol accounted for 94% of the total blood radioactivity at 2 min but only about 6% from 3 to 8 h post dose. 4. Propofol has a volume of distribution equivalent to about 3 to 4 times body weight, and a mean total body clearance of 2.2 1/min.