临床药代动力学和药效学性质的药物用于治疗帕金森病。
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Deleu D, Northway毫克,汉森Y
临床药代动力学和药效学性质的药物用于治疗帕金森病。
Pharmacokinet。2002; 41 (4): 261 - 309。
- PubMed ID
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11978145 (在PubMed]
- 文摘
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当前研究帕金森病(P必威国际appD)的重点是症状性治疗和神经保护干预措施。药物已经用于治疗症状是左旋多巴,通常结合外围脱羧酶抑制剂,合成多巴胺受体受体激动剂,中枢作用antimuscarinic药物金刚烷胺、单胺oxidase-B(缺氧)抑制剂和catechol-O-methyltransferase(转移酶)抑制剂。药物至少有一些证据神经保护作用的特定的多巴胺受体激动剂,金刚烷胺缺氧抑制剂(司立吉林)。左旋多巴仍是最有效的药物治疗PD的。有几个因素导致了左旋多巴的复杂的临床药物动力学:不稳定的吸收,半衰期短,外围O-methylation跨血脑屏障和方便运输。左旋多巴反应患者的波动,浓度效应曲线变得陡峭,转移到正确的患者相比,稳定的反应。Pharmacokinetic-pharmacodynamic造型可以影响治疗策略的决策。多巴胺受体激动剂包括麦角衍生品(溴麦角环肽,培高利特,lisuride卡麦角林),non-ergoline衍生品(pramipexole,罗匹尼罗和吡贝地尔)和阿朴吗啡。大多数的多巴胺受体激动剂有其特定的药理。它们用于单一疗法作为一个兼职在早期和先进的PD左旋多巴。 Few pharmacokinetic and pharmacodynamic data are available regarding centrally acting antimuscarinic drugs. They are characterised by rapid absorption after oral intake, large volume of distribution and low clearance relative to hepatic blood flow, with extensive metabolism. The mechanism of action of amantadine remains elusive. It is well absorbed and widely distributed. Since elimination is primarily by renal clearance, accumulation of the drug can occur in patients with renal dysfunction and dosage reduction must be envisaged. The COMT inhibitors entacapone and tolcapone dose-dependently inhibit the formation of the major metabolite of levodopa, 3-O-methyldopa, and improve the bioavailability and reduce the clearance of levodopa without significantly affecting its absorption. They are useful adjuncts to levodopa in patients with end-of-dose fluctuations. The MAO-B inhibitor selegiline may have a dual effect: reducing the catabolism of dopamine and limiting the formation of neurotoxic free radicals. The pharmacokinetics of selegiline are highly variable; it has low bioavailability and large volume of distribution. The oral clearance is many-fold higher than the hepatic blood flow and the drug is extensively metabolised into several metabolites, some of them being active. Despite the introduction of several new drugs to the antiparkinsonian armamentarium, no single best treatment exists for an individual patient with PD. Particularly in the advanced stage of the disease, treatment should be individually tailored.
