Table 6.
Pharmacokinetic parameters for levormeloxifene after administration of multiple oral doses. Data are presented as mean (± s.d.). NA: insufficient data for estimation of t1/2; Numbers in brackets represent the range. After 35 and 56 days of dosing at least the final nine and three (or more) sampling points were used for the estimation of λz, respectively.
| Levormeloxifene dose | ||||||
|---|---|---|---|---|---|---|
| 30 days of dosing (part 1) | 56 days of dosing (part 2) | |||||
| 20 mg | 80 mg | 160 mg | 40 mg | 80 mg | ||
| Cmax (ng ml−1) | 1st dose | 71 ± 10 | 387 ± 98 | 769 ± 256 | 182 ± 48 | 377 ± 58 |
| last dose | 254 ± 74 | 1081 ± 328 | 2031 ± 618 | 477 ± 146 | 879 ± 229 | |
| tmax (h) | 1st dose | 3.00 ± 1.55 | 1.85 ± 1.16 | 1.83 ± 1.17 | 2.42 ± 2.23 | 2.00 ± 1.53 |
| last dose | 3.17 ± 3.06 | 5.60** ± 10.29 | 2.51 ± 2.07 | 1.50 ± 1.24 | 2.01 ± 1.54 | |
| t1/2* (days) | 1st dose | NA | NA | NA | NA | NA |
| last dose | 5.9 (5.0–7.0) | 5.4 (4.6–7.0) | 5.5 (4.3–6.3) | 5.1 (3.6–8.4) | 4.8 (3.2–7.9) | |
| AUC(0, τ) (µg ml−1 h) | 1st dose | 1.0 ± 0.2 | 4.8 ± 0.9 | 9.0 ± 2.4 | 2.4 ± 0.4 | 4.9 ± 0.8 |
| last dose | 4.7 ± 1.4 | 19.8 ± 8.5 | 33.4 ± 10.5 | 8.5 ± 2.6 | 15.2 ± 4.2 | |
| RA | actual | 4.7 ± 0.9 | 3.9 ± 1.2 | 3.7 ± 0.4 | 3.5 ± 0.9 | 3.1 ± 0.7 |
| theoretical | 9.1 ± 1.0 | 8.6 ± 1.8 | 8.6 ± 1.0 | 8.3 ± 2.0 | 7.9 ± 2.0 | |
*
harmonic mean+(min-max).
**
tmax value is 5.60 h due to a single outlier of 24 h.