Pharmacokinetic parameters of MGS0028 in Sprague-Dawley rats, rhesus monkeys, and beagle dogs
Results are presented as mean (±S.D.), n = 3, except for dog at 0.1 mg/kg p.o., where n = 2.
Parameter | Sprague-Dawley Rat | Rhesus Monkey | Beagle Dog | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 3 mg/kg i.v. | 1 mg/kg p.o. | 3 mg/kg p.o. | 10 mg/kg p.o. | 1 mg/kg i.v. | 5 mg/kg p.o. | 0.3 mg/kg i.v. | 0.1 mg/kg p.o. | 0.3 mg/kg p.o. | |||||||
| Cmax (μM) | - | 1.0 ± 0.2 | 2.7 ± 0.3 | 6.0 ± 1.9 | - | 1.0 ± 0.5 | - | 1.5 ± 0.8 | 4.0 ± 1.0 | ||||||
| tmax (h) | - | 0.8 ± 0.2 | 2.0 ± 0.0 | 3.0 ± 1.4 | - | 2.3 ± 1.5 | - | 0.4 ± 0.1 | 0.5 ± 0.0 | ||||||
| AUC0-24 h (μM · h) | 14.3 ± 0.8 | 3.4 ± 0.5 | 9.7 ± 1.2 | 35.8 ± 3.8 | 10.2 + 2.6 | 10.4 ± 5.0 | 8.2 + 1.1 | 1.7 ± 0.9 | 5.7 ± 0.3 | ||||||
| Effective t1/2 (h) | 1.1 | - | - | - | 1.1 | - | 0.9 | - | - | ||||||
| CLp (ml/min/kg) | 16.2 ± 0.9 | - | - | - | 8.0 ± 1.8 | - | 2.8 ± 0.4 | - | - | ||||||
| Vd (l/kg) | 0.5 ± 0.2 | - | - | - | 0.6 ± 0.1 | - | 0.1 ± 0.01 | - | - | ||||||
| F (%) | - | 70.7 | 67.7 | 75.3 | - | 20.3* | - | 63.4 | 69 | ||||||
| AUCMetabolite/AUCParent | 0.8 | 0.4 | 0.6 | 0.3 | 0.3 | 0.9 | 0.0 | 0.0 | 0.0 | ||||||
-, not applicable.
↵* Some monkeys experienced emesis, and this may be partially responsible for low bioavailability.