Auteri A, Mosca A, Lattuada N, Luzzana M, Zecca L, Radice D, Imbimbo B P
Istituto di Patologia Speciale Medica, Università di Siena, Italy.
Eur J Clin Pharmacol. 1993;45(4):373-6. doi: 10.1007/BF00265958.
Eptastigmine is a new cholinesterase inhibitor, which may be potentially useful for the symptomatic treatment of Alzheimer's disease. A preliminary evaluation of its pharmacodynamic and pharmacokinetic profiles in the elderly has now been made in 6 healthy subjects (63-84 years of age) given 30 mg eptastigmine as a single oral dose. Blood was collected prior to and 1, 2, 3, 4, 6, 8, and 12 h after eptastigmine administration for measurement of cholinesterase inhibition in plasma and red blood cells and the plasma drug concentrations. The maximum plasma cholinesterase inhibition was 17%, which was reached 2.7 h after treatment. In red cells the maximum inhibition of the enzyme was 29% after 3.8 h. The estimated half-time of cholinesterase recovery was 12.4 h in plasma and 13.6 h in red blood cells. The peak plasma concentration of eptastigmine of 0.86 ng.ml-1 was reached after 1.4 h. Following absorption the drug was rapidly distributed into tissues (t1/2 alpha = 0.44 h) and then eliminated with a half-life of 12.1 h. The drug was well tolerated in all but one subject, who showed bradycardia with hypertension and nausea for about 2 h after the dose. The results indicate that oral administration of eptastigmine to elderly subjects produces long lasting inhibition of cholinesterase activity in plasma and in red blood cells.
依他斯的明是一种新型胆碱酯酶抑制剂，可能对阿尔茨海默病的症状治疗有潜在作用。现对6名健康受试者（年龄63 - 84岁）单次口服30毫克依他斯的明后的药效学和药代动力学特征进行了初步评估。在依他斯的明给药前及给药后1、2、3、4、6、8和12小时采集血液，以测定血浆和红细胞中的胆碱酯酶抑制情况以及血浆药物浓度。血浆胆碱酯酶最大抑制率为17%，在治疗后2.7小时达到。在红细胞中，酶的最大抑制率在3.8小时后为29%。血浆中胆碱酯酶恢复的估计半衰期为12.4小时，红细胞中为13.6小时。依他斯的明的血浆峰值浓度在1.4小时后达到0.86纳克·毫升-1。吸收后，药物迅速分布到组织中（t1/2α = 0.44小时），然后以12.1小时的半衰期消除。除一名受试者外，所有受试者对该药物耐受性良好，该受试者在给药后约2小时出现心动过缓、高血压和恶心症状。结果表明，老年受试者口服依他斯的明可对血浆和红细胞中的胆碱酯酶活性产生持久抑制作用。
