Gschwind H P, Schütz H, Wigger N, Bentley P
Research and Development Department, Ciba-Geigy Limited, Basle, Switzerland.
Eur J Drug Metab Pharmacokinet. 1992 Jan-Mar;17(1):67-82. doi: 10.1007/BF03189990.
The absorption and disposition of the nootropic drug oxiracetam (4-hydroxy-2-oxo-pyrrolidine-1-yl acetamide) were studied in rats and dogs (10 mg/kg i.v. and 10, 50 and 3000 mg/kg p.o.) and two healthy male volunteers (800 mg p.o.) using a [14C]-labelled preparation. Peroral absorption of [14C]-oxiracetam was incomplete in rats (28-42%), high in dogs (81-90%) and intermediate in man (about 56%). The rate of absorption was high in all species. Elimination was biphasic and the concentration of total radioactivity in blood and plasma declined rapidly with an initial elimination half-life of 1-3 h in all species. The specific systemic exposure to [14C]-oxiracetam was lowest in the rat, intermediate in the dog and highest in man. In all species the systemically available radioactivity was nearly exclusively excreted in urine in the form of unmetabolized oxiracetam. Whole-body autoradiography and quantitative determination of the radioactivity in various organs following i.v. and p.o. administration of [14C]-oxiracetam to rats demonstrated extensive distribution of the compound with high levels in kidney, liver, lung and skin, and very low levels in the brain. The radioactivity was rapidly eliminated from the body and minimal accumulation was observed upon repeated administration of 10 mg/kg for 8 days. Levels in the brain were still low, but higher than following a single dose, indicating slow diffusion across the blood-brain barrier. In pregnant rats treated with [14C]-oxiracetam radioactivity passed reversibly and to a limited extent through the placenta into fetal tissue.
使用[14C]标记制剂，在大鼠和犬（静脉注射10mg/kg，口服10、50和3000mg/kg）以及两名健康男性志愿者（口服800mg）中研究了促智药奥拉西坦（4-羟基-2-氧代-吡咯烷-1-基乙酰胺）的吸收和处置情况。[14C] - 奥拉西坦在大鼠中的口服吸收不完全（28 - 42%），在犬中较高（81 - 90%），在人体中处于中等水平（约56%）。所有物种的吸收速率都很高。消除呈双相，所有物种血液和血浆中总放射性浓度迅速下降，初始消除半衰期为1 - 3小时。[14C] - 奥拉西坦的特定全身暴露在大鼠中最低，在犬中处于中等水平，在人体中最高。在所有物种中，全身可利用的放射性几乎完全以未代谢的奥拉西坦形式经尿液排泄。对大鼠静脉注射和口服[14C] - 奥拉西坦后进行的全身放射自显影以及各器官放射性的定量测定表明，该化合物分布广泛，在肾脏、肝脏、肺和皮肤中含量较高，而在脑中含量极低。放射性从体内迅速消除，在以10mg/kg重复给药8天期间观察到极少的蓄积。脑中的水平仍然很低，但高于单次给药后，表明其穿过血脑屏障的扩散缓慢。在用[14C] - 奥拉西坦治疗的怀孕大鼠中，放射性可逆地且在有限程度上通过胎盘进入胎儿组织。
