Table 1.
Active moiety pharmacokinetics at steady state following 4- and 8-mg once daily doses of fesoterodine vs. tolterodine extended release (ER)
| Tolterodine ER 4 mg | Tolterodine ER 8 mg | Fesoterodine 4 mg | Fesoterodine 8 mg | |||||
|---|---|---|---|---|---|---|---|---|
| Tolterodine | 5-HMT | Tolterodine + 5-HMT | Tolterodine | 5-HMT | Tolterodine + 5-HMT | 5-HMT | 5-HMT | |
| Parameter (units)* | EMs (n = 18) | EMs (n = 18) | EMs (n = 18) | EMs (n = 18) | ||||
| AUC(0,24 h) (nm h) (%CV) | 61.1 (116) | 66.1 (42) | 138.1 (83) | 139.1 (120) | 141.2 (42) | 299.8 (87) | 91.7 (46) | 179.6 (42) |
| Cmax (nm) (%CV) | 5.6 (120) | 5.2 (41) | 11.6 (87) | 13.5 (106) | 10.7 (43) | 25.8 (81) | 8.8 (48) | 16.4 (40) |
| tmax (h) (range) | 5 (2, 12) | 5 (2, 6) | 5 (2, 6) | 5 (1, 12) | 4.5 (3, 12) | 4 (1, 6) | 5 (2, 6) | 5 (4, 6) |
| Ae (mg) (%CV) | NA† | 0.38 (39) | NA† | NA† | 0.71 (30) | NA† | 0.44 (40) | 0.89 (36) |
| CLr (ml min−1) (%CV) | NA† | 259 (25) | NA† | NA† | 235 (29) | NA† | 214 (27) | 225 (24) |
| PMs (n = 10) | PMs (n = 10) | PMs (n = 9) | PMs (n = 8) | |||||
|---|---|---|---|---|---|---|---|---|
| AUC(0,24 h) (nm h) (%CV) | 601.7 (47) | NA‡ | 601.7 (47) | 1417.9 (44) | NA‡ | 1421.8 (44) | 136.0 (32) | 314.3 (29) |
| Cmax (nm) (%CV) | 35.7 (46) | NA‡ | 35.7 (46) | 80.9 (40) | NA‡ | 81.2 (40) | 11.9 (33) | 26.5 (27) |
| tmax (h) (range) | 5.5 (5, 8) | NA‡ | 5.5 (5, 8) | 6 (4, 12) | NA‡ | 6 (4, 12) | 5 (4, 6) | 5 (4, 6) |
| Ae (mg) (%CV) | NA† | NA‡ | NA† | NA† | NA‡ | NA† | 0.60 (30) | 1.32 (25) |
| CLr (ml min−1) (%CV) | NA† | NA‡ | NA† | NA† | NA‡ | NA† | 207 (38) | 199 (24) |
*
Geometric mean (%CV) for AUC(0,24 h), Cmax, and CLr; arithmetic mean (%CV) for Ae, and median (range) for tmax. Tolterodine and 5-HMT concentrations were expressed in nm units, using their molecular weights (325.5 and 341.5 respectively).
†
Urine samples were not assayed for tolterodine.
‡
5-HMT not formed in PMs following tolterodine ER administration; quantifiable but very low (<0.5 ng ml−1) concentrations in some PMs at the 8-mg dose. EM, extensive metabolizer; 5-HMT, 5-hydroxymethyl tolterodine; PM, poor metabolizer; NA, Not applicable.