Ford J M, Truman C A, Wilcock G K, Roberts C J
University Department of Medicine, Bristol Royal Infirmary, England.
Clin Pharmacol Ther. 1993 Jun;53(6):691-5. doi: 10.1038/clpt.1993.91.
To assess the value of serum measurements of tacrine hydrochloride and its metabolite in predicting risk of adverse reaction in Alzheimer's disease.
The study was an outpatient-based controlled clinical trial. Study subjects were 35 female and 31 male patients who were receiving 50 to 150 mg tacrine hydrochloride per day.
Serum concentration of tacrine hydrochloride and ratio of tacrine hydrochloride to metabolite were significantly higher in the 45 patients with symptomatic adverse effects (p < 0.001). The tacrine hydrochloride to metabolite ratio was significantly higher (p < 0.05) in the 30 patients in whom abnormal liver function developed, but concentration of tacrine hydrochloride was not significantly higher. Women showed a higher incidence of adverse effects (p < 0.05), and tacrine hydrochloride concentrations were higher (p < 0.05). Tacrine hydrochloride concentration and tacrine hydrochloride to metabolite ratio were higher in both men and women in whom adverse effects developed.
Tacrine hydrochloride concentration is valuable in predicting the development of adverse effects, and its measurement may improve the use of the drug.
评估血清中盐酸他克林及其代谢物的测定值在预测阿尔茨海默病不良反应风险方面的价值。
该研究是一项基于门诊的对照临床试验。研究对象为35名女性和31名男性患者，他们每天接受50至150毫克盐酸他克林治疗。
45名出现症状性不良反应的患者中，盐酸他克林的血清浓度以及盐酸他克林与代谢物的比率显著更高（p < 0.001）。30名出现肝功能异常的患者中，盐酸他克林与代谢物的比率显著更高（p < 0.05），但盐酸他克林的浓度没有显著升高。女性的不良反应发生率更高（p < 0.05），且盐酸他克林浓度更高（p < 0.05）。出现不良反应的男性和女性中，盐酸他克林浓度以及盐酸他克林与代谢物的比率均更高。
盐酸他克林浓度在预测不良反应的发生方面具有价值，对其进行测定可能会改善该药物的使用。
