Azevedo Kauppila Linda, Pimenta Silva Daniela, Ferreira Joaquim J
Department of Neurosciences and Mental Health, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
CNS - Campus Neurológico, Torres Vedras, Portugal.
Degener Neurol Neuromuscul Dis. 2021 May 11;11:29-40. doi: 10.2147/DNND.S256722. eCollection 2021.
Parkinson's disease (PD) is a prevalent neurodegenerative disorder, and levodopa (L-dopa) remains the most efficacious drug treatment for PD and a gold-standard for symptom control. Nonetheless, a significant majority of PD patients develop motor fluctuations over their disease course, with a significant impact on quality-of-life, meaning control of such complications translates into a fundamental clinical need. Catechol-O-methyl transferase (COMT) inhibitors (COMT-i) are used as first-line adjuvant therapy to L-dopa for end-of-dose (EoD) motor fluctuations, since they increase L-dopa availability in the brain by inhibiting its peripheral metabolism. Opicapone (OPC), a once-daily, long-acting COMT-i, is the most recent and potent of its class, having been licensed in Europe in 2016 as an add-on to preparations of L-dopa/DOPA decarboxylase inhibitors in PD patients with EoD motor fluctuations. More recently, it has also received approval in the USA and Japan in 2020. Two high-quality positive efficacy studies (double-blind Phase III clinical trials) established OPC efficacy with significant reduction in OFF time (average 60 minutes vs placebo), without concomitant increase of distressing dyskinesias during ON time. These beneficial effects were sustained in open-label extension studies, without unexpected safety issues or adverse events, with dyskinesia having been the most frequent complaint. OPC also avoids liver toxicity and gastrointestinal issues compared with previous COMT-i. In this review, we aimed to cover OPC's lifecycle (synthesis to commercialization), its clinical pharmacological data, safety, tolerability and pharmacovigilance evidence, and discuss its role in the management of motor fluctuations in PD as well as its emerging place in international recommendations.
帕金森病（PD）是一种常见的神经退行性疾病，左旋多巴（L-多巴）仍然是治疗PD最有效的药物，也是症状控制的金标准。尽管如此，绝大多数PD患者在病程中会出现运动波动，对生活质量有重大影响，这意味着控制此类并发症已成为一项基本的临床需求。儿茶酚-O-甲基转移酶（COMT）抑制剂（COMT-i）被用作L-多巴治疗剂末（EoD）运动波动的一线辅助治疗药物，因为它们通过抑制L-多巴的外周代谢来增加其在大脑中的可用性。奥匹卡朋（OPC）是一种每日一次的长效COMT-i，是该类药物中最新且最有效的，于2016年在欧洲获批，作为EoD运动波动的PD患者L-多巴/多巴脱羧酶抑制剂制剂的附加药物。最近，它也于2020年在美国和日本获得批准。两项高质量的阳性疗效研究（双盲III期临床试验）证实了OPC的疗效，显著减少了关期时间（与安慰剂相比平均减少60分钟），且在开期期间不会伴随令人痛苦的异动症增加。这些有益效果在开放标签扩展研究中得以持续，没有出现意外的安全问题或不良事件，异动症是最常见的主诉。与之前的COMT-i相比，OPC还可避免肝毒性和胃肠道问题。在本综述中，我们旨在涵盖OPC的生命周期（从合成到商业化）、其临床药理学数据、安全性、耐受性和药物警戒证据，并讨论其在PD运动波动管理中的作用以及在国际推荐中的新地位。
