大鼠血浆和脑脊液中2-氨基-7-磷酸庚酸酯的药代动力学测定。

Determination of the pharmacokinetics of 2-amino-7-phosphonoheptanoate in rat plasma and cerebrospinal fluid.

作者信息

Compton R P, Hood W F, Monahan J B

机构信息

Central Nervous System Diseases Research, G.D. Searle & Company, St. Louis, MO 63198.

出版信息

Neurosci Lett. 1988 Feb 3;84(3):339-44. doi: 10.1016/0304-3940(88)90532-0.

DOI:10.1016/0304-3940(88)90532-0

PMID:3352960

Abstract

The pharmacokinetics of 2-amino-7-phosphonoheptanoate (AP7) in rat plasma and appearance in cerebrospinal fluid (CSF) are reported. Using high-performance liquid chromatography (HPLC) with fluorescence detection, concentrations of AP7 can be detected as low as 1.0 microM. Peak CSF concentrations (12-15 microM) for both the D-AP7 and D,L-AP7 are observed 10-15 min after i.v. administration and amount to approximately 0.1% of a 1 mmol/kg dose. Significant quantities (3 microM) are present in CSF at 2 h and no AP7 is detectable at 4 h. Following i.v. administration, a monoexponential clearance was observed for D-AP7 clearance from plasma, 15.4 +/- 0.8 S.E.M. ml/min/kg with a t1/2 of 38.9 +/- 0.8 S.E.M. min. However, a biexponential clearance from plasma was observed for D,L-AP7.

摘要

本文报道了2-氨基-7-膦酰庚酸（AP7）在大鼠血浆中的药代动力学以及其在脑脊液（CSF）中的出现情况。使用带荧光检测的高效液相色谱（HPLC），可检测到低至1.0微摩尔的AP7浓度。静脉注射后10 - 15分钟观察到D-AP7和D,L-AP7的脑脊液峰值浓度（12 - 15微摩尔），约占1毫摩尔/千克剂量的0.1%。2小时时脑脊液中存在大量（3微摩尔），4小时时未检测到AP7。静脉注射后，观察到D-AP7从血浆中的清除呈单指数清除，清除率为15.4±0.8标准误毫升/分钟/千克，半衰期为38.9±0.8标准误分钟。然而，观察到D,L-AP7从血浆中的清除呈双指数清除。