Boucher B A, Foster T S, Phillips B A, Fleck R J, Kirksey D F, Cato A E
Drug Product Evaluation Unit, College of Pharmacy, University of Kentucky, Lexington.
J Clin Pharmacol. 1987 Feb;27(2):151-4. doi: 10.1002/j.1552-4604.1987.tb02176.x.
BW 942C hydrochloride is an enkephalin analogue that has exhibited a wide separation between antidiarrheal dosages and dosages inducing adverse effects in animals. This has likewise been the case in humans when administered orally. In this study, the safety and tolerance of single 0.5-mg doses of intravenous BW 942C compared with placebo were assessed in humans. Four healthy male volunteers received BW 942C, and two received placebo. The effects of BW 942C on serum growth hormone (GH), luteinizing hormone (LH), prolactin (PR), and follicle-stimulating hormone (FSH) were assessed in three of these volunteers. No significant changes were apparent in vital signs, in clinical chemistry, hematologic and urine studies following BW 942C administration. BW 942C did not appear to alter mood as assessed by two psychologic mood scales. Prolactin levels tended to increase in volunteers receiving BW 942C two hours postinfusion. Luteinizing hormone concentrations decreased slightly at two and six hours. No trends in FSH or GH could be identified. Pulmonary function testing did not reveal any significant changes in oximetry, spirometry, or plethysmography in any of the subjects. A marked decrease in CO2 responsiveness in two subjects may indicate that BW 942C has mild ventilatory depressant effects. Untoward effects experienced in volunteers receiving BW 942C included heaviness in the limbs, nasal stuffiness, mouth dryness, facial flushing, skin rash, and prickling sensations. These effects bear a striking similarity to those experienced after parenteral administration of other enkephalin analogues. Intravenous administration of BW 942C up to 0.5 mg appears safe from a laboratory, physiologic, and clinical perspective with unusual untoward effects that may preclude rational use of the drug by the parenteral route.
盐酸BW 942C是一种脑啡肽类似物，在动物实验中，其止泻剂量与产生不良反应的剂量之间有很大差异。口服给药时，在人体中情况也是如此。在本研究中，评估了人体静脉注射单剂量0.5毫克BW 942C与安慰剂相比的安全性和耐受性。四名健康男性志愿者接受了BW 942C，两名接受了安慰剂。其中三名志愿者评估了BW 942C对血清生长激素（GH）、促黄体生成素（LH）、催乳素（PR）和促卵泡激素（FSH）的影响。给予BW 942C后，生命体征、临床化学、血液学和尿液检查均未出现明显变化。通过两种心理情绪量表评估，BW 942C似乎并未改变情绪。接受BW 942C的志愿者在输注两小时后催乳素水平有升高趋势。促黄体生成素浓度在两小时和六小时时略有下降。未发现FSH或GH有任何趋势变化。肺功能测试未显示任何受试者的血氧饱和度、肺活量测定或体积描记法有任何显著变化。两名受试者的二氧化碳反应性明显降低，这可能表明BW 942C有轻度的通气抑制作用。接受BW 942C的志愿者出现的不良反应包括肢体沉重、鼻塞、口干、面部潮红、皮疹和刺痛感。这些效应与其他脑啡肽类似物经肠胃外给药后所经历的效应极为相似。从实验室、生理和临床角度来看，静脉注射高达0.5毫克的BW 942C似乎是安全的，但有不寻常的不良反应，这可能会妨碍通过肠胃外途径合理使用该药物。
