Ford_1993_Clin.Pharmacol.Ther_53_691

OBJECTIVE: To assess the value of serum measurements of tacrine hydrochloride and its metabolite in predicting risk of adverse reaction in Alzheimer's disease.
METHODS: 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.
RESULTS: 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. CONCLUSION: Tacrine hydrochloride concentration is valuable in predicting the development of adverse effects, and its measurement may improve the use of the drug.