Department for Parkinson Disease, IRCCS San Camillo, Venice, Italy.
Expert Opin Drug Metab Toxicol. 2011 Oct;7(10):1307-14. doi: 10.1517/17425255.2011.614232. Epub 2011 Sep 6.
Immediate-release (IR) pramipexole dihydrochloride is indicated for the treatment of signs and symptoms of idiopathic Parkinson's disease (PD). It is administered alone (without levodopa) or in combination with levodopa, during the entire progress of the disease, up to an advanced stage. Currently, it is also indicated for the treatment of moderate-to-severe primary restless legs syndrome (RLS). An extended-release (ER) formulation of pramipexole has been developed to allow a once-daily administration and to provide more stable dopaminergic stimulation in PD patients.
This review summarizes the overall pharmacokinetic profile of pramipexole for both the IR and ER formulations. Also discussed are the clinically relevant determinants of pramipexole peripheral pharmacokinetics and the potential role of genetic and clinical determinants in drug efficacy.
Pramipexole is a non-ergot agonist with selective affinity for dopamine receptors of the D2 subfamily, in particular D3. Pramipexole has a very low affinity for serotoninergic 5-HT2A and 5-HT2B receptors, as well as D1-type receptors. Furthermore, it does not carry the risk to induce valvular heart disease or pulmonary and retroperitoneal fibrosis, seen with long-term use of the ergot-derived dopamine agonists. The recent introduction of a once-daily formulation poses significant advantages for patients, reflected by relatively stable plasma levels. The most obvious benefit is convenience of use and better adherence to treatment schedule. Additional advantages could include the opportunity to provide more continuous drug delivery in a fashion that could help minimize dyskinesia risk, if the drug is used early in the disease course.
盐酸普拉克索速释片用于治疗特发性帕金森病（PD）的体征和症状。它在疾病的整个过程中单独使用（无左旋多巴）或与左旋多巴联合使用，直至晚期。目前，它也被用于治疗中度至重度原发性不安腿综合征（RLS）。已开发出普拉克索的延长释放（ER）制剂，以允许每日一次给药，并为 PD 患者提供更稳定的多巴胺能刺激。
本综述总结了盐酸普拉克索速释和 ER 制剂的总体药代动力学特征。还讨论了普拉克索外周药代动力学的临床相关决定因素以及遗传和临床决定因素在药物疗效中的潜在作用。
普拉克索是一种非麦角类激动剂，对多巴胺受体 D2 亚家族具有选择性亲和力，特别是 D3。普拉克索对 5-羟色胺能 5-HT2A 和 5-HT2B 受体以及 D1 型受体的亲和力非常低。此外，它不会像长期使用麦角衍生的多巴胺激动剂那样导致瓣膜性心脏病或肺和腹膜后纤维化。最近推出的每日一次制剂为患者带来了显著优势，反映在相对稳定的血浆水平上。最明显的好处是使用方便，更能遵守治疗计划。如果在疾病早期使用该药物，还可能具有提供更连续药物输送的机会，从而有助于最大限度地降低运动障碍风险。
