Aden-Abdi Y, Villén T, Ericsson O, Gustafsson L L, Dahl-Puustinen M L
Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.
Bull World Health Organ. 1990;68(6):731-6.
Metrifonate concentrations in plasma, its inhibition of blood cholinesterase, and side-effects were studied in 16 healthy volunteers who received a single oral dose of 2.5, 5, 7.5 or 15 mg/kg in a randomized double-blind study (4 subjects for each dose). Metrifonate was determined by a gas chromatographic method. Peak plasma levels were reached within 2 hours; the half-life in plasma, oral clearance, and normalized Cmax and AUCs did not differ significantly between the four groups. Plasma cholinesterase (BuchE) was inhibited to low levels in all subjects, while erythrocyte cholinesterase (AchE) was affected in a dose-dependent fashion. The occurrence of side-effects correlated strongly with peak plasma levels but not with maximum AchE inhibition or with increase in salivation. This study shows that the absorption of metrifonate was not significantly different for doses between 2.5 and 15 mg/kg. The plasma levels of this drug correlated with the occurrence of side-effects.
在一项随机双盲研究中，对16名健康志愿者进行了研究，这些志愿者单次口服2.5、5、7.5或15mg/kg的剂量（每个剂量组4名受试者），研究了血浆中敌百虫的浓度、其对血液胆碱酯酶的抑制作用以及副作用。采用气相色谱法测定敌百虫。2小时内达到血浆峰值水平；四组之间血浆半衰期、口服清除率以及标准化的Cmax和AUCs无显著差异。所有受试者的血浆胆碱酯酶（丁酰胆碱酯酶）均被抑制至低水平，而红细胞胆碱酯酶（乙酰胆碱酯酶）受到剂量依赖性影响。副作用的发生与血浆峰值水平密切相关，但与最大乙酰胆碱酯酶抑制或唾液分泌增加无关。本研究表明，2.5至15mg/kg剂量的敌百虫吸收无显著差异。该药物的血浆水平与副作用的发生相关。
