PF-5081090 (8.75, 75, 300 mg/kg; s.c.; single dose) exhibits a exposure increasing in linear manner across the dose range in mice, with area under the concentration-time curve (AUC) and maximum concentration of drug in serum (Cmax) increasing with a proportional increase in dose[1].
PF-5081090 shows potent efficacies against sentinel strains of P. aeruginosa and K. pneumonia in CD-1 mice, with effective dose (ED50) ranging from 7.4-55.9 mg/kg (against acute septicemia model), <25 mg/kg (against pneumonia model), and 16.8 mg/kg (against neutropenic thigh model) in mice infected with P. aeruginosa PA-1950[1].
Pharmacokinetics of PF-5081090 in CD-1 micea[1]
| Dose (mg/kg) | Cmax (mg/L) | Tmax (h) | AUC (h mg/L) | Free AUC (h mg/L) | T1/2 (h) | CL (L/h/kg) | Vss (L/kg) |
| 18.75 | 5.02 | 0.25 | 5.09 | 1.58 | 0.6 | 3.79 | 2.20 |
| 75 | 15.50 | 0.33 | 17.60 | 5.46 | 0.69 | 4.32 | 3.30 |
| 300 | 75.40 | 0.33 | 76.30 | 23.70 | 0.68 | 3.92 | 2.53 |
a Following single subcutaneous doses.
