LeWitt Peter A
Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Neurology. 2004 Mar 23;62(6 Suppl 4):S8-11. doi: 10.1212/wnl.62.6_suppl_4.s8.
Apomorphine is a non-narcotic morphine derivative that acts as a potent dopaminergic agonist. Its high first-pass hepatic metabolism prevents effectiveness by the oral route; instead, subcutaneous injection is the usual route, and intranasal, sublingual, rectal, and iontophoretic transdermal delivery has been investigated for the treatment of Parkinson's disease (PD). The rate of uptake after subcutaneous injection is influenced by factors such as location, temperature, depth of injection, and body fat. Studies have shown the latency of onset to clinical effect after s.c. injection ranged from 7.3 to 14 minutes. Cerebrospinal fluid T(max)lags behind plasma T(max) by 10 to 20 minutes. Considerable intersubject variability is found with pharmacokinetic variables; in some studies there are five- to tenfold differences in C(max)and area-under-the-concentration-time-curve seen in PD patients. Apomorphine metabolism occurs through several enzymatic pathways, including N-demethylation, sulfation, glucuronidation, and catechol-O-methyltransferase as well as by nonenzymatic oxidation. The complexities of apomorphine uptake, distribution, and clearance probably contribute to its variability of clinical actions.
阿扑吗啡是一种非麻醉性吗啡衍生物，作为一种强效多巴胺能激动剂发挥作用。其较高的首过肝脏代谢使其口服无效；相反，皮下注射是常用途径，鼻内、舌下、直肠和离子导入透皮给药已被研究用于治疗帕金森病（PD）。皮下注射后的吸收速率受注射部位、温度、注射深度和体脂等因素影响。研究表明，皮下注射后临床起效的潜伏期为7.3至14分钟。脑脊液T(max)比血浆T(max)滞后10至20分钟。在药代动力学变量方面存在相当大的个体间差异；在一些研究中，帕金森病患者的C(max)和浓度-时间曲线下面积存在5至10倍的差异。阿扑吗啡通过多种酶促途径代谢，包括N-去甲基化、硫酸化、葡萄糖醛酸化和儿茶酚-O-甲基转移酶以及非酶促氧化。阿扑吗啡吸收、分布和清除的复杂性可能导致其临床作用的变异性。
