Verhoef J, van den Wildenberg H M
Scientific Development Group, Organon International B.V., Oss, The Netherlands.
Eur J Drug Metab Pharmacokinet. 1989 Jul-Sep;14(3):229-34. doi: 10.1007/BF03190103.
After intravenous dosing in dogs [3H-Lys9]-DE gamma E (Org 5878) was very rapidly eliminated from the circulation. Disappearance of the neuropeptide from blood followed a biphasic decay with half-lives of 0.6 +/- 0.1 min (+/- S.D.; alpha-phase) and 2.4 +/- 1.0 min (beta-phase). The central volume of distribution ranged between 0.05 and 0.23 l.kg-1. The mean blood clearance rate amounted to 0.15 l.min-1.kg-1, which is indicative of extensive hepatic and extrahepatic metabolism of DE gamma E. In contrast to intravenous dosing, subcutaneous injection of [3H]-DE gamma E in dogs resulted in low but relatively long-lasting peptide levels in blood. Peak values were found at 5-10 min, whereafter they declined to the limit of detection at 1.5-2 h. The bioavailability of DE gamma E for this route of administration was shown to be 20-23%.
在犬类中静脉注射[3H-赖氨酸9]-DEγE（Org 5878）后，其从循环系统中消除的速度非常快。神经肽从血液中的消失呈双相衰减，α相半衰期为0.6±0.1分钟（±标准差），β相半衰期为2.4±1.0分钟。中央分布容积在0.05至0.23升·千克-1之间。平均血液清除率为0.15升·分钟-1·千克-1，这表明DEγE在肝脏和肝外有广泛的代谢。与静脉注射不同，犬类皮下注射[3H]-DEγE后，血液中的肽水平较低但持续时间相对较长。在5至10分钟时出现峰值，之后在1.5至2小时下降至检测限。经此给药途径，DEγE的生物利用度为20%至23%。
