Lautenschlager Marion, Heinz Andreas
Department of Psychiatry & Psychotherapy, Charité-Universitätsmedizin Berlin, Charité Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.
Expert Rev Neurother. 2008 Feb;8(2):193-200. doi: 10.1586/14737175.8.2.193.
Paliperidone-extended release (ER) is an antipsychotic medication newly introduced in the USA and Europe in 2007. It is the first oral atypical antipsychotic with an extended release, which is achieved by the osmotic-controlled release oral delivery system (OROS), a well-established technology already in use for CNS drugs (e.g., methylphenidate and hydromorphone). Paliperidone was in the focus of investigations for years, as it is the major metabolite (9-hydroxyrisperidone) of the widely used atypical antipsychotic risperidone. Paliperidone-ER has demonstrated clinical efficacy, safety and good tolerability on a once-daily basis in three randomized, double-blind, placebo-controlled, 6-week-studies including patients with acute schizophrenia and one randomized, double-blind, placebo-controlled long-term study assessing recurrence of psychotic symptoms in patients with schizophrenia. Key features are predominant renal elimination, therefore low risk of interaction with other drugs, good efficacy against psychotic symptoms based on D2-receptor and 5HT2A-receptor antagonism and very low affinity for muscarinic receptors resulting in absence of anticholinergic side effects. The OROS-ER technology leads to considerably lower plasma peak levels compared with nonextended-release formulations, thus possibly reducing side effects.
帕利哌酮缓释片于2007年在美国和欧洲首次推出，是一种抗精神病药物。它是首个采用渗透控释口服给药系统（OROS）实现缓释的口服非典型抗精神病药物，OROS是一项已应用于中枢神经系统药物（如哌甲酯和氢吗啡酮）的成熟技术。多年来，帕利哌酮一直是研究的重点，因为它是广泛使用的非典型抗精神病药物利培酮的主要代谢产物（9-羟基利培酮）。在三项针对急性精神分裂症患者的随机、双盲、安慰剂对照、为期6周的研究以及一项评估精神分裂症患者精神病症状复发情况的随机、双盲、安慰剂对照长期研究中，帕利哌酮缓释片已证明每日一次给药具有临床疗效、安全性和良好的耐受性。其主要特点是主要经肾脏排泄，因此与其他药物相互作用的风险较低；基于D2受体和5HT2A受体拮抗作用，对精神病症状有良好疗效；对毒蕈碱受体亲和力极低，因而无抗胆碱能副作用。与非缓释制剂相比，OROS缓释技术可使血浆峰浓度大幅降低，从而可能减少副作用。
