Pharmacokinetic parameters in blood after intravenous and oral administration of donepezil, tacrine, and galantamine
Values represent means ± S.D. n = 3 except for donepezil old group (n = 5). For the galantamine intravenously dosed young group (n = 2), both values are shown. Tmax is expressed as median and range. Fp.o. was calculated for galantamine-dosed young rat 3 using average AUCi.v. from young rat 1 and 2.
| Parameters | Donepezil | Tacrine | Galantamine | |||
|---|---|---|---|---|---|---|
| Young | Old | Young | Old | Young | Old | |
| Intravenous | ||||||
| Cmax (μM) | 0.32 ± 0.04 | 0.30 ± 0.02 | 0.70 ± 0.06 | 0.74 ± 0.07 | 0.59, 0.69 | 0.91 ± 0.07* |
| CLb (ml per min/kg) | 52 ± 7 | 43 ± 5 | 93 ± 9 | 77 ± 8 | 44, 41 | 34 ± 6 |
| Vd (l/kg) | 9.2 ± 0.6 | 11.8 ± 0.8** | 5.1 ± 0.5 | 5.2 ± 0.7 | 5.5, 5.0 | 2.9 ± 0.1** |
| t1/2 (h) | 2.5 ± 0.3 | 3.6 ± 0.3** | 0.9 ± 0.2 | 1.1 ± 0.1 | 1.9, 1.9 | 1.2 ± 0.4 |
| MRT (h) | 3.0 ± 0.4 | 4.6 ± 0.5** | 0.9 ± 0.2 | 1.1 ± 0.1 | 2.1, 2.0 | 1.5 ± 0.3 |
| AUC(0–t)/dose (min · kg/l) | 15.9 ± 1.7 | 16.4 ± 1.6 | 10.2 ± 1.0 | 12.4 ± 1.4 | 20.4, 21.8 | 28.9 ± 4.6 |
| AUC0–∞/dose (min · kg/l) | 19.5 ± 2.9 | 23.7 ± 3.0 | 10.8 ± 1.0 | 13.0 ± 1.2 | 22.7, 24.1 | 29.9 ± 5.3 |
| % extrapolation | 18 ± 3 | 30 ± 3 | 5 ± 2 | 5 ± 2 | 10, 10 | 7 ± 3 |
| Oral | ||||||
| Cmax (μM) | 0.18 ± 0.06 | 0.20 ± 0.02 | 0.36 ± 0.13 | 0.31 ± 0.08 | 0.89 ± 0.06 | 1.33 ± 0.40 |
| Tmax (h) | 1.0 (0.5–1.5) | 1.0 (0.5–4.1) | 0.5 (0.5–1.0) | 0.5 (0.5–1.0) | 0.5 (0.5–0.5) | 0.5 (0.5–1.3) |
| AUC(0–t) (μM · h) | 0.76 ± 0.27 | 0.91 ± 0.09 | 0.70 ± 0.15 | 0.89 ± 0.08 | 2.89 ± 0.38 | 3.45 ± 0.53 |
| AUCt/dose (min · kg/l) | 5.8 ± 2.1 | 6.9 ± 0.8 | 2.8 ± 0.6 | 3.5 ± 0.3 | 17.4 ± 2.3 | 19.3 ± 2.6 |
| Fp.o. (%) | 36 ± 10 | 43 ± 8 | 27 ± 7 | 29 ± 2 | 83 ± 13 | 67 ± 10 |