Serum concentrations of tacrine hydrochloride predict its adverse effects in Alzheimer's disease.
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.


CONCLUSIONS
Tacrine hydrochloride concentration is valuable in predicting the development of adverse effects, and its measurement may improve the use of the drug.
University Department of Medicine, Bristol Royal Infirmary, England.
J M
JM
Ford
C A
CA
Truman
G K
GK
Wilcock
C J
CJ
Roberts
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D013619:Tacrine / Q000009:adverse effects* / Q000097:blood* / Q000378:metabolism
D013619:Tacrine