Table 1.
Steady-state pharmacokinetic parameters of donepezil (Noetzli and Eap 2013)
| Parameter | Donepezil |
|---|---|
| Daily dose (mg) | 5–10, 23a |
| Bioavailability (%) | 100 |
| Protein binding (%) | 93 |
| t1/2 (h) | 70b |
| tmax,ss (h) | 4 (IR), 6 (SR) |
| Cmax,ss (ng/mL) | 61 ± 10 (10 mg/day), 129 (CV 29 %) (23 mg/day)a |
| AUCmax,ss (ng h/mL) | 1128 ± 196 (10 mg/day)c |
| CLtot (L/h) | 10 ± 2.5c |
| Vd (L/kg) | 11 ± 2c |
| Metabolism | Hepatic (CYP2D6, CYP3A4, UGT) |
| Kinetics | Linear |
| Steady state (days) | 14–21 |
AUC ss area under the concentration–time curve at steady state, cap capsule; CL tot total systemic clearance, C max,ss maximum steady-state plasma drug concentration during a dosage interval, CV coefficient of variation, CYP cytochrome P450, ER extended-release formulation, IR immediate-release formulation, SR sustained-release formulation, t ½ elimination half-life, t max,ss time to reach Cmax,ss UGT uridine 50-diphosphoglucuronosyltransferase, V d apparent volume of distribution
aThe new dosage of 23 mg has recently been approved by the US FDA for the treatment of moderate-to-severe Alzheimer’s disease
bThe t½ of the drug is short, but the duration of action is longer because acetylcholinesterase and butyrylcholinesterase are inhibited for 8.5 and 3.5 h, respectively, through a pseudoirreversible mechanism
cMean ± standard deviation or range