Table 2.
Effect of food on ODN pharmacokinetic parameters following administration of single oral doses of ODN of 25, 100 and 200 mg to young healthy male subjects
| PK parameter | Comparison (fed/fasted)† | Comparison (fed/fasted) | ||
|---|---|---|---|---|
| 25 mg high-fat meal | 100 mg high-fat meal | 200 mg high-fat meal | 100 mg low-fat meal | |
| AUC0–24 h (μm h) * | 2.11 (1.56, 2.85) | 1.73 (1.37, 2.18) | 1.87 (1.46, 2.40) | 1.25 (0.94, 1.66) |
| AUC0–168 h (μm h)* | ND | 1.40 (1.00, 1.95) | ND | 1.28 (0.97, 1.68) |
| AUC0–∞ (μm h)* | ND | ND | ND | 1.39 (0.98, 1.98) |
| C24 h (nm)* | 2.10 (1.58, 2.80) | 2.30 (1.58, 3.34) | 1.87 (1.42, 2.45) | 1.2 (0.89, 1.63) |
| C168 h (nm)* | ND | 0.95 (0.44, 2.07) | ND | 1.44 (0.98, 2.13) |
| Cmax, day1 (nm)* | 2.23 (1.56, 3.18) | 1.76 (1.37, 2.24) | 1.82 (1.39, 2.40) | 1.20 (0.82, 1.74) |
| Cmax, overall (nm)* | 2.36 (1.67, 3.34) | 1.76, (1.37, 2.24) | ND | 1.20 (0.82, 1.74) |
| Apparent terminal half-life (h)‡ | ND | 48.2 (11.7) | 50.5 (13.4) | 75.9 (36.9) |
Abbreviations are as follows: CI, confidence interval; AUC0-24 h, aea under the curve0-24 hours; AUC0-168 h, area under the curve0-168 hours; AUC0-∞, area under the curve0-infinity; C24 h, concentration at 24 hours; C168 h, concentration at 168 hours; Cmax,day1, maximum concentration, day1; ND, not determined; ODN, odanacatib Tmax,day1, time to maximum plasma concentration, day 1.
Back-transformed least-squares mean and 90% CI from mixed-effects model performed on natural log-transformed values.
Comparison at 25 mg ODN was made from within subjects, and comparisons at 100 and 200 mg ODN were made from between subjects.
Harmonic mean, jack-knife SD.