Metabolism of haloperidol to pyridinium species in patients receiving high doses intravenously: Is HPTP an intermediate?
Metabolism of haloperidol to pyridinium species in patients receiving high doses intravenously: Is HPTP an intermediate?
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DOI：
10.1016/s0024-3205(97)00955-7
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发表时间：
1997-11-07
期刊：
影响因子：
6.1
通讯作者：
Pond, SM
中科院分区：
文献类型：
--
作者：
Avent, KM;Riker, RR;Pond, SM
已在人体中证实氟哌啶醇（HP）代谢为潜在神经毒性的吡啶类物质HPP+和RHPP+。从各种动物种属中收获的微粒体的体外研究表明，四氢吡啶类化合物HPTP和RHPTP可能是该途径中的中间体。然而，这尚未在人体内得到证实。在这项研究中，血浆和尿液收集8例重症患者治疗高剂量静脉HP进行了分析HPTP和RHPTP使用高效液相色谱电化学检测。然而，无论是HPTP或RHPTP检测尽管HP和RHP的血浆浓度高于任何以前的报告。HPP+和RHPP+均以高浓度存在于尿液中，分别占HP给药剂量的1.1 +/- 0.5%和5.3 +/-3.6%。HPP+和RHPP+的表观消除半衰期分别为67.3 +/- 11.0 h和63.3 +/- 11.6 h。血浆和尿液中不存在HPTP和RHPTP表明，在人体中，这些四氢吡啶类化合物或者是HP体内代谢中不重要的中间体，或者仅短暂存在于其形成部位，不会释放到循环中。
The metabolism of haloperidol (HP) to the potentially neurotoxic pyridinium species, HPP+ and RHPP+, has been demonstrated in humans. In vitro studies in microsomes harvested from various animal species indicate that the tetrahydropyridines, HPTP and RHPTP, could be intermediates in this pathway. However, this has not yet been demonstrated in vivo in humans. In this study, plasma and urine collected from eight critically ill patients treated with high doses of intravenous HP were analyzed for HPTP and RHPTP using HPLC with electrochemical detection. However, neither HPTP nor RHPTP were detected despite plasma concentrations of HP and RHP higher than any previously reported. HPP+ and RHPP+ were both present in the urine in high concentrations and accounted for 1.1 +/- 0.5% and 5.3 +/- 3.6%, respectively, of the administered dose of HP. The apparent elimination half-lives of HPP+ and RHPP+ were 67.3 +/- 11.0 hr and 63.3 +/- 11.6 hr, respectively. The absence of HPTP and RHPTP in plasma and urine suggests that in humans these tetrahydropyridines either are insignificant intermediates in the metabolism of HP in vivo or are present only transiently at their site of formation and are not released into the circulation.