Cedarbaum J M
Cornell University Medical College, Burke Rehabilitation Center, White Plains, New York.
Clin Pharmacokinet. 1987 Sep;13(3):141-78. doi: 10.2165/00003088-198713030-00002.
Of the neurological disorders, none can claim a battery of therapeutic agents based upon as rational a pharmacology as can Parkinson's disease. In this review, the clinical pharmacokinetics of the major classes of anti-Parkinsonian drugs is discussed. Although they are the oldest drugs in the anti-Parkinsonian armamentarium, little pharmacokinetic data are available regarding the anticholinergic and antihistaminic agents. Based on elimination half-lives of 10 to 18 hours, most could probably be effectively given on a twice-daily schedule. Amantadine is unique among anti-Parkinsonian agents both in lacking a clearly defined mechanism of action and in being eliminated from the body exclusively by renal excretion of unchanged drug. Thus the normal decline of renal function in the elderly Parkinsonian population becomes an important factor in avoiding potential drug toxicity. The pharmacokinetics and pharmacodynamics of levodopa are complex. Since it is an amino acid, it follows metabolic pathways and must compete for absorption and brain uptake with a number of large neutral amino acids. It has a short elimination half-life and, as Parkinson's disease progresses, the brain loses its capacity to store the drug and becomes dependent in a moment-to-moment fashion on plasma levodopa concentrations, creating therapeutic response fluctuations in over 50% of patients. Pharmacokinetic considerations in the management of these response fluctuations are discussed. The newest class of anti-Parkinsonian agents are the direct acting dopamine receptor agonists. These drugs, all derivatives of ergot, have more prolonged durations of anti-Parkinsonian action than levodopa. However, other than bromocriptine, clinical experience with members of this class of drugs is still limited.
在神经系统疾病中，没有哪种疾病能像帕金森病那样，拥有一系列基于合理药理学的治疗药物。在这篇综述中，将讨论主要几类抗帕金森病药物的临床药代动力学。尽管抗胆碱能药和抗组胺药是抗帕金森病药物中使用时间最长的，但关于它们的药代动力学数据却很少。根据10至18小时的消除半衰期，大多数药物可能每日给药两次就能有效。金刚烷胺在抗帕金森病药物中独具特色，它既缺乏明确的作用机制，又仅通过肾脏以原形药物排泄的方式从体内消除。因此，老年帕金森病患者肾功能的正常衰退成为避免潜在药物毒性的一个重要因素。左旋多巴的药代动力学和药效学很复杂。由于它是一种氨基酸，它遵循代谢途径，并且必须与许多中性大氨基酸竞争吸收和进入大脑。它的消除半衰期很短，而且随着帕金森病的进展，大脑储存药物的能力丧失，变得时刻依赖血浆左旋多巴浓度，导致超过50%的患者出现治疗反应波动。文中讨论了在处理这些反应波动时的药代动力学考虑因素。最新一类抗帕金森病药物是直接作用的多巴胺受体激动剂。这些药物都是麦角衍生物，其抗帕金森病作用的持续时间比左旋多巴更长。然而，除了溴隐亭之外，这类药物成员的临床经验仍然有限。
