a Instituto de Investigaciones Cardiológicas , University of Buenos Aires, National Research Council (ININCA-UBA-CONICET) , Buenos Aires , Argentina.
b Department of Physiology , School of Medicine, University of Buenos Aires (UBA) , Buenos Aires , Argentina.
Expert Opin Pharmacother. 2019 Apr;20(6):635-645. doi: 10.1080/14656566.2019.1574746. Epub 2019 Feb 7.
L-threo-3,4-dihydroxyphenylserine (droxidopa), a pro-drug metabolized to norepinephrine in nerve endings and other tissues, has been commercially available in Japan since 1989 for treating orthostatic hypotension symptoms in Parkinson's disease (PD) patients with a Hoehn & Yahr stage III rating, as well as patients with Multiple System Atrophy (MSA), familial amyloid polyneuropathy, and hemodialysis. Recently, the FDA has approved its use in symptomatic neurogenic orthostatic hypotension (NOH). Areas covered: The authors review the effects of droxidopa in NOH with a focus on the neurodegenerative diseases PD, MSA, and pure autonomic failure (PAF). Expert opinion: A few small and short placebo-controlled clinical trials in NOH showed significant reductions in the manometric drop in blood pressure (BP) after posture changes or meals. Larger Phase III studies showed conflicting results, with two out of four trials meeting their primary outcome and thus suggesting a positive yet short-lasting effect of the drug on OH Questionnaire composite score, light-headedness/dizziness score, and standing BP during the first two treatment-weeks. Results appear essentially similar in PD, MSA, and PAF. The FDA granted droxidopa approval in the frame of an 'accelerated approval program' provided further studies are conducted to assess its long-term effects on OH symptoms.
L-苏-3,4-二羟基苯丙氨酸（Droxidopa），一种前体药物，在神经末梢和其他组织中代谢为去甲肾上腺素，自 1989 年以来在日本商业化用于治疗帕金森病（PD）患者的直立性低血压症状，Hoehn 和 Yahr 分期为 III 期，以及多发性系统萎缩（MSA）、家族性淀粉样多神经病和血液透析患者。最近，FDA 批准其用于治疗症状性神经源性直立性低血压（NOH）。
作者回顾了 Droxidopa 在 NOH 中的作用，重点关注神经退行性疾病 PD、MSA 和单纯自主神经衰竭（PAF）。
几项关于 NOH 的小型短期安慰剂对照临床试验表明，体位改变或进食后血压（BP）的测压下降明显减少。更大规模的 III 期研究结果相互矛盾，四项试验中有两项达到了主要终点，因此表明该药物对 OH 问卷综合评分、头晕/眩晕评分和前两周站立时 BP 有积极但短暂的影响。在 PD、MSA 和 PAF 中，结果基本相似。FDA 在“加速批准计划”框架内批准 Droxidopa，前提是进行进一步研究以评估其对 OH 症状的长期影响。
