Therapeutic drug monitoring for patients with Alzheimer dementia to improve treatment with donepezil.
BACKGROUND
Aiming to verify that therapeutic drug monitoring has the potential to optimize treatment with acetylcholine esterase inhibitors of patients with Alzheimer dementia, this study investigated whether serum concentrations of donepezil are associated with clinical improvement.


METHODS
Clinical improvement was measured using the clinical global impression (CGI) scale, and donepezil concentrations were measured in serum by a high-performance liquid chromatographic method with spectrophotometric detection.


RESULTS
In total, 206 serum samples from 106 patients (49.5% female) were retrospectively available for analysis. Patients included were treated under everyday conditions. Their mean ± SD age was 72 ± 9 years, daily doses of donepezil were 5 and 10 mg, and their mean ± SD serum concentrations were 23 ± 9 and 47 ± 18 ng/mL, respectively. Serum concentrations correlated significantly (P < 0.001) with CGI scores (Pearson's correlation coefficient r = 0.511, P < 0.01). In patients who were "very much improved," according to their CGI score, the mean serum concentration was 66 ± 20 ng/mL and thus significantly higher (P < 0.01) than in patients with "minimal improvement" (29 ± 12 ng/mL). Receiver operating characteristics analysis suggests that donepezil serum concentrations of at least 50 ng/mL may be recommended for maximal clinical benefit.


CONCLUSIONS
Because donepezil serum concentrations were highly variable between individual patients and the majority of patients exhibited concentrations that were below 50 ng/mL at therapeutic doses of 5 and 10 mg/d, it can be concluded that therapeutic drug monitoring may be used to enhance the effectiveness of donepezil treatment.
*Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center; and †Department of Psychiatry and Psychotherapy, University Medical Center, Mainz, Germany.
Gudrun
G
Hefner
Anne
A
Brueckner
Christoph
C
Hiemke
Andreas
A
Fellgiebel
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000097:blood / Q000627:therapeutic use; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007189:Indans / Q000097:blood* / Q000627:therapeutic use*; D008297:Male; D010880:Piperidines / Q000097:blood* / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil