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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Pharmacokinetics, pharmacodynamics, and safety of metrifonate in patients with Alzheimer's disease.
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Pharmacokinetics, pharmacodynamics, and safety of metrifonate in patients with Alzheimer's disease.

机译：甲吗啡酯在阿尔茨海默氏病患者中的药代动力学，药效学和安全性。

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摘要

Metrifonate is converted nonenzymatically to 2.2, dimethyl dichlorovinyl phosphate (DDVP), an inhibitor of acetylcholinesterase (AChE). This 21-day, randomized, double-blind, placebo-controlled trial of metrifonate in patients with Alzheimer's disease (n = 27) evaluated four doses, each administered orally once daily. All patients received a loading dose (LD) for 6 days followed by a maintenance dose (MD) for 15 days. The treatment groups were: panel 1, LD = 1.5 mg/kg (75-135 mg), MD = 0.25 mg/kg (12.5-25 mg); panel 2, LD = 2.5 mg/kg (125-225 mg), MD = 0.40 mg/kg (20-35 mg); panel 3, LD = 4.0 mg/kg (200-335 mg), MD = 0.65 mg/kg (30-60 mg); and panel 4, LD = 4.0 mg/kg (200-335 mg), MD = 1.0 mg/kg (50-90 mg). All metrifonate doses were well tolerated. Most adverse events were mild to moderate in intensity, gastrointestinal in nature, and transient. Mean area under the concentration-time curve (AUC) and maximum concentration (Cmax) for both metrifonate and DDVP increased in relation to dose. Metrifonate and DDVP had similar, largely dose-independent mean values for time to Cmax (tmax) and half-life (t1/2). There was little or no accumulation of either metrifonate or DDVP with long-term administration. After 21 days of treatment, mean percent erythrocyte AChE inhibition was 14%, 35%, 66%, 77%, and 82% for placebo and panels 1 through 4, respectively. Cognitive improvement was observed with the two highest metrifonate doses. These results reflect favorable safety and pharmacokinetic profiles for the use of metrifonate in the treatment of Alzheimer's disease.
机译：甲磷酰胺以非酶法转化为2.2，二甲基二氯乙烯基磷酸酯（DDVP），一种乙酰胆碱酯酶（AChE）的抑制剂。这项21天的美甲芬酯在阿尔茨海默氏病（n = 27）患者中的随机，双盲，安慰剂对照试验评估了四剂，每剂每天口服一次。所有患者均接受6天的负荷剂量（LD），然后接受15天的维持剂量（MD）。治疗组为：第一组，LD = 1.5 mg / kg（75-135 mg），MD = 0.25 mg / kg（12.5-25 mg）;第2组，LD = 2.5 mg / kg（125-225 mg），MD = 0.40 mg / kg（20-35 mg）;第3组，LD = 4.0 mg / kg（200-335 mg），MD = 0.65 mg / kg（30-60 mg）;图4，LD ＝ 4.0mg / kg（200-335mg），MD ＝ 1.0mg / kg（50-90mg）。所有甲米芬剂量均耐受良好。大多数不良事件为轻度至中度，胃肠道性质和短暂的。甲磺酸酯和DDVP的浓度-时间曲线（AUC）和最大浓度（Cmax）下的平均面积均与剂量有关。 Metrifonate和DDVP的Cmax（tmax）和半衰期（t1 / 2）时间具有相似的，很大程度上与剂量无关的平均值。长期给药几乎没有或完全没有残留甲米芬或DDVP。治疗21天后，安慰剂和第1至第4组的平均红细胞AChE抑制百分比分别为14％，35％，66％，77％和82％。服用两次最高的甲磺酸甲磺酸酯可观察到认知改善。这些结果反映了使用甲吗啡酯治疗阿尔茨海默氏病的有利安全性和药代动力学特征。

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