Table 1.
Plasma PK of unbound (−)-SPD in rats
| PK parameter | i.v. 2 mg·kg−1 |
p.o. |
||
|---|---|---|---|---|
| 20 mg·kg−1 | 50 mg·kg−1 | 100 mg·kg−1 | ||
| Male rats | ||||
| AUC0→12 h (h·ng·mL−1) | 120 ± 45 | 19.2 ± 4.9 | 27.6 ± 7.6 | 49.2 ± 24.9 |
| MRT (h) | 1.40 ± 0.35 | 5.05 ± 1.75 | 3.22 ± 0.52 | 4.85 ± 1.57 |
| T1max (h) | – | 0.22 ± 0.10 | 0.75 ± 0.25 | 0.58 ± 0.22 |
| C1max (ng·mL−1) | 341 ± 114a | 3.12 ± 1.68 | 4.35 ± 1.33 | 2.29 ± 0.44 |
| T2max (h) | 8.67 ± 1.15 | 8.67 ± 0.67 | 7.33 ± 1.33 | 10.0 ± 0.0 |
| C2max (ng·mL−1) | 2.11 ± 1.33 | 2.62 ± 1.30 | 3.70 ± 0.20 | 7.17 ± 3.55 |
| t11/2 (h) (i.v., 0–1 h) | 0.15 ± 0.03 | – | – | – |
| t21/2 (h) (i.v., 1–6 h; p.o. 1–4 h) | 0.75 ± 0.14 | 1.22 ± 0.25 | 1.07 ± 0.16 | 1.73 ± 0.99 |
| CL (L·h−1·kg−1) | 24.1 ± 10.7 | – | – | – |
| Vss (L·kg−1) | 25.3 ± 3.9 | – | – | – |
| F (%) | – | 1.60 ± 0.41 | 0.92 ± 0.25 | 0.82 ± 0.42 |
| Female rats | ||||
| AUC0→12 h (h·ng·mL−1) | 244 ± 161 | 9.78 ± 2.09 | 28.2 ± 10.1 | 66.2 ± 8.9 |
| MRT (h) | 2.51 ± 0.17 | 4.01 ± 0.78 | 4.22 ± 1.02 | 4.31 ± 0.05 |
| T1max (h) | – | 0.14 ± 0.06 | 0.14 ± 0.06 | 0.25 ± 0.00 |
| C1max (ng·mL−1) | 362 ± 146a | 3.25 ± 1.04 | 3.59 ± 1.45 | 13.8 ± 4.6 |
| T2max (h) | 8.00 ± 0.00 | 10.0 ± 0.00 | 8.00 ± 1.16 | 8.67 ± 0.67 |
| C2max (ng·mL−1) | 7.26 ± 5.76 | 1.44 ± 0.38 | 3.11 ± 0.89 | 6.50 ± 1.88 |
| t11/2 (h) (i.v., 0–1 h) | 0.33 ± 0.06 | – | – | – |
| t21/2 (h) (i.v., 1–6 h; p.o. 1–4 h) | 0.92 ± 0.09 | 1.07 ± 0.23 | 1.74 ± 0.26 | 1.05 ± 0.17 |
| CL (L·h−1·kg−1) | 11.5 ± 4.7 | – | – | – |
| Vss (L·kg−1) | 35.8 ± 23.7 | – | – | – |
| F (%) | – | 0.40 ± 0.09 | 0.46 ± 0.17 | 0.54 ± 0.07 |
All values are given as mean ± SEM (n= 3).
(−)-SPD, (−)-stepholidine; AUC, area under concentration–time curve; CL, total plasma clearance; MRT, mean residence time; PK, pharmacokinetics; Vss, distribution volume at steady status.
a
The highest measured concentration at 5 min after i.v. administration.