Estimated exposures of peliglitazar and its acyl glucuronide in mice, rats, monkeys, and humans after a single oral dose of peliglitazar
| Study | Analyte | Species | Doses | Conc.c at 1 h | Conc. Exposure Multiplesa | AUC0–t | AUC Exposure Multiplesa |
|---|---|---|---|---|---|---|---|
| mg/kg | μM | μM · h | |||||
| Radiolabeled ADME | Peliglitazar | Mouse | 30 | 59.58 | 397 | 247.4 | 333 |
| Rat | 15 | 4.51 | 30 | 17.6 | 24 | ||
| Monkey | 3 | 3.64 | 24 | 15.5 | 21 | ||
| Humanb | 10 | 0.15 | 1 | 0.74 | 1 | ||
| Radiolabeled ADME | Peliglitazar AG | Mouse | 30 | 1.18 | 6.4 | 4.72 | 3.84 |
| Rat | 15 | 0.07 | 0.4 | 0.21 | 0.17 | ||
| Monkey | 3 | 0.34 | 1.8 | 1.45 | 1.18 | ||
| Humanb | 10 | 0.18 | 1 | 1.23 | 1 | ||
| Long-term toxicity studiesd,e | Peliglitazar AG | Mouse | 250 | 9.8 | 54 | 39.3 | 31.9 |
| Rat | 300 | 1.4 | 7.8 | 4.2 | 3.41 | ||
| Monkey | 2.5 | 0.28 | 1.6 | 1.21 | 1.0 | ||
| Carcinogen studiese,f | Peliglitazar AG | Mouse | 10 | 0.39 | 2.2 | 1.57 | 1.28 |
| Rat | 30 | 0.14 | 0.7 | 0.42 | 0.34 |
ADME, absorption, distribution, metabolism, and excretion.
↵a Exposure multiples were calculated by dividing Cmax or AUC values in animals by that in humans.
↵b Data are milligrams per subject.
↵c Concentration is estimated from the relative distribution of the parent or acyl glucuronide metabolites in the plasma, the total concentration of radioactivity, and the specific activity of the administered drug; AUC0–t is estimated from the concentration in plasma at limited time points (1, 4, and 12 h) using the trapezoidal rule.
↵d Doses are the highest dose from the 6-month rat, 3-month mouse, and 1-year monkey toxicology studies.
↵e Concentration and AUC values are scaled linearly with regard to dose values in ADME studies.
↵f Highest projected doses for the carcinogenicity studies.