Pharmacokinetic Parameters Measured for SANORG 34006 and SR 90107 After IV or SC Administration to Rats, Rabbits, and Baboons
| . | Species . | Dose (nmol/kg) . | Tmax (h) . | Cmax (nmol/mL) . | t1/2 (h) . | AUC(0-∞) (h · nmol/mL) . | Clearance (mL/kg · h) . | Distribution Volume (mL/kg) . |
|---|---|---|---|---|---|---|---|---|
| IV | ||||||||
| SR 90107/ORG 31540 | Rat | 100 | 0.08 ± 0 | 1.2 ± 0.8 | 0.7 ± 0.1 | 1.5 ± 0.1 | 23 ± 8 | 123 ± 12 |
| SANORG 34006 | Rat | 100 | 0.08 ± 0 | 2.3 ± 0.3 | 9.2 ± 1.8 | 11.2 ± 2.5 | 12.8 ± 2.4 | 109 ± 41 |
| SR 90107/ORG 31540 | Rabbit | 100 | 0.08 ± 0 | 1.6 ± 0.1 | 2.9 ± 1.4 | 3.4 ± 1.4 | 31.3 ± 7.7 | 104 ± 15 |
| SANORG 34006 | Rabbit | 100 | 0.08 ± 0 | 2.2 ± 0.4 | 22.8 ± 2.0 | 30 ± 9 | 3.5 ± 0.9 | 117 ± 35 |
| SR 90107/ORG 31540 | Baboon | 100 | 0.5 ± 0 | 1.0 ± 0.1 | 4.7 ± 0.9 | 6.1 ± 0.4 | 18.1 ± 2.9 | 122 ± 17 |
| SANORG 34006 | Baboon | 100 | 0.5 ± 0 | 1.6 ± 0.1 | 61.9 ± 7.4 | 62.6 ± 5.3 | 1.6 ± 0.1 | 143 ± 10 |
| SC | ||||||||
| SR 90107/ORG 31540 | Rat | 100 | 0.6 ± 0.3 | 0.6 ± 0.2 | 1.6 ± 0.4 | 1.7 ± 0.3 | 61 ± 9 | 131 ± 17 |
| SANORG 34006 | Rat | 100 | 2.1 ± 0.2 | 0.87 ± 0.01 | 14.7 ± 2.9 | 12.3 ± 0.3 | 8.1 ± 0.1 | 172 ± 34 |
| SR 90107/ORG 31540 | Rabbit | 100 | 2 ± 0 | 0.8 ± 0.1 | 3.3 ± 0.4 | 5.5 ± 0.6 | 16.3 ± 0.4 | 79 ± 10 |
| SANORG 34006 | Rabbit | 30 | 4.3 ± 3.3 | 0.33 ± 0 | 22.7 ± 4.2 | 12.2 ± 1.4 | 2.5 ± 0.3 | 80 ± 7 |
| SANORG 34006 | Rabbit | 100 | 3.4 ± 1.9 | 1.61 ± 0.1 | 16.8 ± 2.5 | 35 ± 10 | 3.2 ± 1.1 | 76 ± 13 |
| SANORG 34006 | Rabbit | 300 | 5.7 ± 4.1 | 4.85 ± 1.7 | 20.8 ± 6 | 140 ± 77 | 2.6 ± 1.1 | 74 ± 19 |
| SR 90107/ORG 31540 | Baboon | 100 | 1.7 ± 1.2 | 0.5 ± 0.1 | 5.4 ± 1.2 | 4.7 ± 0.8 | 21.6 ± 3.8 | 144 ± 25 |
| SANORG 34006 | Baboon | 100 | 1 ± 0 | 0.9 ± 0.1 | 60.4 ± 4.9 | 45.3 ± 4.1 | 2.2 ± 0.2 | 193 ± 17 |
| . | Species . | Dose (nmol/kg) . | Tmax (h) . | Cmax (nmol/mL) . | t1/2 (h) . | AUC(0-∞) (h · nmol/mL) . | Clearance (mL/kg · h) . | Distribution Volume (mL/kg) . |
|---|---|---|---|---|---|---|---|---|
| IV | ||||||||
| SR 90107/ORG 31540 | Rat | 100 | 0.08 ± 0 | 1.2 ± 0.8 | 0.7 ± 0.1 | 1.5 ± 0.1 | 23 ± 8 | 123 ± 12 |
| SANORG 34006 | Rat | 100 | 0.08 ± 0 | 2.3 ± 0.3 | 9.2 ± 1.8 | 11.2 ± 2.5 | 12.8 ± 2.4 | 109 ± 41 |
| SR 90107/ORG 31540 | Rabbit | 100 | 0.08 ± 0 | 1.6 ± 0.1 | 2.9 ± 1.4 | 3.4 ± 1.4 | 31.3 ± 7.7 | 104 ± 15 |
| SANORG 34006 | Rabbit | 100 | 0.08 ± 0 | 2.2 ± 0.4 | 22.8 ± 2.0 | 30 ± 9 | 3.5 ± 0.9 | 117 ± 35 |
| SR 90107/ORG 31540 | Baboon | 100 | 0.5 ± 0 | 1.0 ± 0.1 | 4.7 ± 0.9 | 6.1 ± 0.4 | 18.1 ± 2.9 | 122 ± 17 |
| SANORG 34006 | Baboon | 100 | 0.5 ± 0 | 1.6 ± 0.1 | 61.9 ± 7.4 | 62.6 ± 5.3 | 1.6 ± 0.1 | 143 ± 10 |
| SC | ||||||||
| SR 90107/ORG 31540 | Rat | 100 | 0.6 ± 0.3 | 0.6 ± 0.2 | 1.6 ± 0.4 | 1.7 ± 0.3 | 61 ± 9 | 131 ± 17 |
| SANORG 34006 | Rat | 100 | 2.1 ± 0.2 | 0.87 ± 0.01 | 14.7 ± 2.9 | 12.3 ± 0.3 | 8.1 ± 0.1 | 172 ± 34 |
| SR 90107/ORG 31540 | Rabbit | 100 | 2 ± 0 | 0.8 ± 0.1 | 3.3 ± 0.4 | 5.5 ± 0.6 | 16.3 ± 0.4 | 79 ± 10 |
| SANORG 34006 | Rabbit | 30 | 4.3 ± 3.3 | 0.33 ± 0 | 22.7 ± 4.2 | 12.2 ± 1.4 | 2.5 ± 0.3 | 80 ± 7 |
| SANORG 34006 | Rabbit | 100 | 3.4 ± 1.9 | 1.61 ± 0.1 | 16.8 ± 2.5 | 35 ± 10 | 3.2 ± 1.1 | 76 ± 13 |
| SANORG 34006 | Rabbit | 300 | 5.7 ± 4.1 | 4.85 ± 1.7 | 20.8 ± 6 | 140 ± 77 | 2.6 ± 1.1 | 74 ± 19 |
| SR 90107/ORG 31540 | Baboon | 100 | 1.7 ± 1.2 | 0.5 ± 0.1 | 5.4 ± 1.2 | 4.7 ± 0.8 | 21.6 ± 3.8 | 144 ± 25 |
| SANORG 34006 | Baboon | 100 | 1 ± 0 | 0.9 ± 0.1 | 60.4 ± 4.9 | 45.3 ± 4.1 | 2.2 ± 0.2 | 193 ± 17 |
Means ± SD (n = 4 to 9).