Gal J, Zirrolli J A, Lichtenstein P S
Division of Clinical Pharmacology, School of Medicine, University of Colorado Health Sciences Center, Denver.
Res Commun Chem Pathol Pharmacol. 1988 Oct;62(1):3-17.
Previous studies on the metabolic fate of antihypertensive agent labetalol in humans identified only conjugated metabolites of the drug and accounted for only a portion of the dose. In this study, urine samples obtained from three patients on chronic labetalol therapy for hypertension were analyzed initially by thin layer chromatography for the presence of other metabolites. All three urine samples were found to contain 3-amino-1-phenylbutane. The identify of this metabolite in one of the urine samples was confirmed by electron capture negative-ion chemical ionization mass spectrometry. The mass spectrometry experiments also identified the presence in the urine sample of the D-hydroxy derivative of 3-amino-1-phenylbutane. The two metabolites are the result of oxidative biotransformations of labetalol. 3-Amino-1-phenylbutane has been reported to be a potent sympathomimetic agent, and the question arises whether the newly identified metabolites of labetalol contribute to its pharmacological effects.
先前关于抗高血压药物拉贝洛尔在人体中的代谢命运的研究仅鉴定出该药物的结合代谢物，且仅解释了一部分剂量。在本研究中，最初通过薄层色谱法分析了从三名接受拉贝洛尔长期治疗高血压的患者获得的尿液样本，以检测其他代谢物的存在。发现所有三个尿液样本均含有3-氨基-1-苯基丁烷。通过电子捕获负离子化学电离质谱法确认了其中一个尿液样本中这种代谢物的身份。质谱实验还鉴定出尿液样本中存在3-氨基-1-苯基丁烷的D-羟基衍生物。这两种代谢物是拉贝洛尔氧化生物转化的结果。据报道，3-氨基-1-苯基丁烷是一种有效的拟交感神经药，因此产生了一个问题，即新鉴定出的拉贝洛尔代谢物是否对其药理作用有贡献。
