PDF(Pubmed)
Abstract：
UNASSIGNED: Parkinson\'s disease (PD) is characterized by striatal dopamine deficiency. Since dopamine cannot cross the digestive and blood-brain barriers, its precursor, levodopa (L-DOPA), remains the mainstay of treatment. However, the significant pharmacokinetic (Pk) and pharmacodynamic (Pd) limitations of L-DOPA, combined with the severity of PD, may trigger motor and non-motor complications, for which continuous dopaminergic delivery therapies have been developed.
UNASSIGNED: The aim of this study was to review the literature on the Pk/Pd limitations of L-DOPA and how current treatments of continuous dopaminergic administration ameliorate these problems, in order to identify the need for new therapeutic avenues.
UNASSIGNED: A comprehensive literature search was carried out using PubMed and 75 articles were initially extracted. Following independent screening by two reviewers and consideration of eligibility, 10 articles were chosen for further analysis. Information concerning the Pk/Pd of L-DOPA was classified for each article.
UNASSIGNED: Pk/Pd problems notably include: (i) restricted digestive and cerebral absorption; (ii) unnecessary peripheral distribution; (iii) short half-life; (iv) age- and PD-induced decline of central aromatic L-amino acid decarboxylase; (v) misdistribution in many cells; and (vii) pulsatile stimulation of dopaminergic receptors. Current treatments only slightly ameliorate some of these problems.
UNASSIGNED: Many Pk/Pd constraints are not resolved by existing continuous dopaminergic delivery therapies. This highlights the significant gap between these treatments and the ideal of continuous dopaminergic stimulation.
UNASSIGNED: The aim of this study was to review the literature on the Pk/Pd limitations of L-DOPA and how current treatments of continuous dopaminergic administration ameliorate these problems, in order to identify the need for new therapeutic avenues.
UNASSIGNED: A comprehensive literature search was carried out using PubMed and 75 articles were initially extracted. Following independent screening by two reviewers and consideration of eligibility, 10 articles were chosen for further analysis. Information concerning the Pk/Pd of L-DOPA was classified for each article.
UNASSIGNED: Pk/Pd problems notably include: (i) restricted digestive and cerebral absorption; (ii) unnecessary peripheral distribution; (iii) short half-life; (iv) age- and PD-induced decline of central aromatic L-amino acid decarboxylase; (v) misdistribution in many cells; and (vii) pulsatile stimulation of dopaminergic receptors. Current treatments only slightly ameliorate some of these problems.
UNASSIGNED: Many Pk/Pd constraints are not resolved by existing continuous dopaminergic delivery therapies. This highlights the significant gap between these treatments and the ideal of continuous dopaminergic stimulation.
摘要：
■帕金森病（PD）的特征是纹状体多巴胺缺乏。因为多巴胺不能穿过消化和血脑屏障，它的前身，左旋多巴（L-DOPA），仍然是治疗的支柱。然而,L-DOPA的显着药代动力学（Pk）和药效学（Pd）限制，结合PD的严重程度，可能引发运动和非运动并发症，已经开发了连续的多巴胺能递送疗法。
■本研究的目的是回顾有关L-DOPA的Pk/Pd限制以及当前连续多巴胺能给药的治疗如何改善这些问题的文献，以确定是否需要新的治疗途径。
■使用PubMed进行了全面的文献检索，最初提取了75篇文章。经过两名审核员的独立筛选和对资格的考虑，选择10篇文章进行进一步分析。关于L-DOPA的Pk/Pd的信息被分类为每篇文章。
■Pk/Pd问题主要包括：（i）消化和大脑吸收受限；（ii）不必要的外周分布；（iii）半衰期短；（iv）年龄和PD诱导的中枢芳香族L-氨基酸脱羧酶下降；（v）在许多细胞中的分布不均；（vii）多巴胺能受体的脉冲刺激。目前的治疗仅稍微改善了这些问题中的一些。
■现有的连续多巴胺能递送疗法不能解决许多Pk/Pd限制。这突出了这些治疗与连续多巴胺能刺激的理想之间的显著差距。
■本研究的目的是回顾有关L-DOPA的Pk/Pd限制以及当前连续多巴胺能给药的治疗如何改善这些问题的文献，以确定是否需要新的治疗途径。
■使用PubMed进行了全面的文献检索，最初提取了75篇文章。经过两名审核员的独立筛选和对资格的考虑，选择10篇文章进行进一步分析。关于L-DOPA的Pk/Pd的信息被分类为每篇文章。
■Pk/Pd问题主要包括：（i）消化和大脑吸收受限；（ii）不必要的外周分布；（iii）半衰期短；（iv）年龄和PD诱导的中枢芳香族L-氨基酸脱羧酶下降；（v）在许多细胞中的分布不均；（vii）多巴胺能受体的脉冲刺激。目前的治疗仅稍微改善了这些问题中的一些。
■现有的连续多巴胺能递送疗法不能解决许多Pk/Pd限制。这突出了这些治疗与连续多巴胺能刺激的理想之间的显著差距。
