Pharmacokinetic parameters of FSM and PROB in cynomolgus monkeys (n = 3) following intravenous administration of PROB alone (40 mg/kg), FSM alone (2 mg/kg), and PROB with FSM
Pharmacokinetic parameters were determined as described in Materials and Methods. Data are shown as mean ± S.D. (n = 3). PROB was intravenously dosed 30 minutes prior to FSM administration in the coadministration treatment group.
| Analyte/Parameter | PROB Alone | FSM Alone | FSM with PROB | Ratio (90% CI) |
|---|---|---|---|---|
| FSM | ||||
| AUC0–24 h (µM⋅h) | NA | 11.5 ± 0.7 | 47.7 ± 5.9** | 4.1 (3.6–4.8) |
| CLTOT (ml/min per kilogram) | NA | 8.8 ± 0.6 | 2.1 ± 0.3*** | 0.24 (0.21–0.28) |
| VdSS (l/kg) | NA | 0.33 ± 0.11 | 0.21 ± 0.03 | 0.66 (0.31–1.4) |
| T1/2 (h) | NA | 5.9 ± 1.4 | 4.7 ± 0.8 | 0.82 (0.40–1.7) |
| CLR (ml/min per kilogram) | NA | 3.7 ± 0.6 | 0.44 ± 0.12** | 0.12 (0.11–0.13) |
| CLNR (ml/min per kilogram) | NA | 5.0 ± 0.6 | 1.7 ± 0.2** | 0.34 (0.27–0.42) |
| ERR | NA | 49.5 ± 8.8 | 5.9 ± 1.4** | 0.12 (0.11–0.13) |
| PROB | ||||
| AUC0–24 h (μM⋅h) | 3436 ± 655 | NA | 3386 ± 860 | 0.98 (0.58–1.6) |
| C24 h (µM) | 7.3 ± 5.7 | NA | 8.9 ± 6.5 | 1.1 (0.37–3.2) |
| CLTOT (ml/min per kilogram) | 0.69 ± 0.12 | NA | 0.71 ± 0.18 | 1.0 (0.60–1.7) |
| VdSS (l/kg) | 0.20 ± 0.01 | NA | 0.21 ± 0.02 | 1.0 (0.85–1.3) |
| T1/2 (h) | 3.7 ± 0.8 | NA | 3.7 ± 0.9 | 1.0 (0.87–1.1) |