Table 3. PKPD Analysis of the Oral LH Inhibition Studiesa.
| Cpd | species | Ki (nM) | LLE | MED (mg/kg) | Tmax (min) | Cplasma,u/Ki | Cbrain,u/Ki | (Cplasma,u/Ki)/MED | (Cbrain,u/Ki)/MED |
|---|---|---|---|---|---|---|---|---|---|
| 2 | rat | 76 | 4.0 | 60 | 150 | 16.4 | 2.32 | 0.273 | 0.039 |
| 2 | monkey | 20 | 4.6 | 20 | 60 | 13.3 | − | 0.665 | − |
| 3 | rat | 219 | 5.2 | 3 | 150 | 22.0 | 5.03 | 7.33 | 1.68 |
| 3 | monkey | 25 | 6.1 | 5 | 90 | 192 | − | 38.4 | − |
| 8 | rat | 22 | 4.6 | 10 | 150 | 15.0 | 12.4 | 1.5 | 1.24 |
| 12 | rat | 2033 | 4.5 | 30 | 150 | 22.5 | 2.77 | 0.75 | 0.09 |
| 16 | rat | 85 | 4.7 | 10 | 150 | 23.8 | 5.87 | 2.38 | 0.59 |
| 17 | rat | 573 | 4.9 | 30 | 45 | 47.3 | 7.71 | 1.58 | 0.26 |
| 18 | rat | 244 | 5.6 | 10 | 45 | 38.9 | 1.82 | 3.89 | 0.18 |
a
Plasma concentrations coincident with LH measurements. MED determined by a significant decrease (p < 0.05) in LH vs baseline with a lower nonsignificant dose established in all cases.