Plasma pharmacokinetic parameters (mean ± S.D.) of total radioactivity after single intravenous and oral doses of 14C-DB289 to rats and cynomolgus monkeys
Parameter | Rat* | Monkey* | ||||
|---|---|---|---|---|---|---|
| Male | Female | Male | Female | |||
| Intravenous | ||||||
| Dose level (mg/kg) | 1 | 1 | 1 | 1 | ||
| Cmax (ng-Eq/ml) | 1030 (167) | 1370 (1250) | 870 (166) | 889 (147) | ||
| AUC∞ (ng-Eq · h/ml) | 1670 | 1750 | 4045a (685) | 4173a (453) | ||
| t1/2 (h) | 5.4 | 1.8 | 46a | 43a | ||
| Oral | ||||||
| Dose level (mg/kg) | 1 | 1 | 1 | 1 | ||
| Cmax (ng-Eq/ml) | 209 (33) | 188 (33) | 70.2 (16.7) | 89.5 (15.9) | ||
| Tmax (h) | 0.75 | 1 | 4 | 1 | ||
| AUC∞ (ng-Eq · h/ml) | 800 | 741 | 1657a (432) | 1269a (370) | ||
| t1/2 (h) | 6.2 | 2.4 | 45.3a | 47.0a | ||
| F (%) | 51 | 45 | 42 | 31 | ||
| Oral | ||||||
| Dose level (mg/kg) | 7.7 | 7.7 | 5 | 5 | ||
| Cmax (ng-Eq/ml) | 1520 (125) | 1080 (199) | 162 (26) | 348 (269) | ||
| Tmax (h) | 2 | 0.5 | 8 | 2 | ||
| AUC∞ (ng-Eq · h/ml) | 6080 | 5520 | 5922a (1197) | 5836 (2037) | ||
| t1/2 (h) | 2.0 | 2.7 | 44.8a | 32.8 | ||
| F (%) | 50 | 43 | 27 | 26 | ||
↵* Concentration and AUC data refer to DB289 free base. Pharmacokinetic parameters for rats were calculated using mean concentration data, and terminal half-life and bioavailability parameters for monkeys were also obtained from mean data; thus, no S.D. values are available in these cases. Oral Tmax for monkeys is the median value.
↵ a Estimated value (linear regression analysis of the terminal decline phase did not meet one or more of the acceptance criteria (see Materials and Methods).