Table 2.
Pharmacokinetic parameters by palovarotene dose and Japanese/non-Japanese group
| Parameter, units | Palovarotene 5 mg | Palovarotene 10 mg | ||||||
|---|---|---|---|---|---|---|---|---|
| Japanese participants (N = 10) | Non-Japanese participants (N = 8) | Japanese participants (N = 10) | Non-Japanese participants (N = 8) | |||||
| AUC(0–∞), h·ng/mL | ||||||||
| Mean ± SD | 222.7 ± 63.5 | 259.9 ± 101.0 | 441.5 ± 103.4 | 484.9 ± 188.5 | ||||
| Minimum, maximum | 134.6, 343.2 | 122.7, 407.7 | 254.1, 546.8 | 242.2, 802.7 | ||||
| AUC(0–z), h·ng/mL | ||||||||
| Mean ± SD | 221.8 ± 62.5 | 259.4 ± 100.9 | 440.3 ± 102.8 | 482.9 ± 189.7 | ||||
| Minimum, maximum | 134.3, 338.2 | 122.3, 406.9 | 254.0, 542.3 | 233.1, 801.4 | ||||
| Cmax, ng/mL | ||||||||
| Mean ± SD | 41.2 ± 17.4 | 41.9 ± 14.1 | 77.2 ± 21.9 | 81.0 ± 23.5 | ||||
| Minimum, maximum | 18.5, 79.9 | 20.5, 64.5 | 41.9, 126.0 | 52.7, 115.0 | ||||
| tmax, h | ||||||||
| Mean ± SD | 4.1 ± 1.1 | 4.0 ± 1.4 | 4.5 ± 1.7 | 4.0 ± 1.4 | ||||
| Minimum, maximum | 3, 6 | 2, 6 | 2, 8 | 2, 6 | ||||
| λz, /h | ||||||||
| Mean ± SD | 0.068 ± 0.016 | 0.062 ± 0.009 | 0.079 ± 0.020 | 0.060 ± 0.018 | ||||
| Median | 0.072 | 0.060 | 0.084 | 0.066 | ||||
| Minimum, maximum | 0.038, 0.085 | 0.048, 0.077 | 0.031, 0.101 | 0.025, 0.079 | ||||
| t½, h | ||||||||
| Mean ± SD | 10.9 ± 3.3 | 11.4 ± 1.7 | 9.7 ± 4.6 | 13.0 ± 6.3 | ||||
| Median | 9.6 | 11.6 | 8.2 | 10.6 | ||||
| Minimum, maximum | 8.2, 18.4 | 9.1, 14.4 | 6.9, 22.4 | 8.8, 27.9 | ||||
| CL/F, L/h | ||||||||
| Mean ± SD | 24.2 ± 7.1 | 22.7 ± 10.4 | 24.1 ± 7.1 | 24.0 ± 10.4 | ||||
| Median | 22.7 | 17.0 | 21.6 | 21.2 | ||||
| Minimum, maximum | 14.6, 37.2 | 12.3, 40.7 | 18.3, 39.4 | 12.5, 41.2 | ||||
| Vd/F, L | ||||||||
| Mean ± SD | 365.6 ± 106.7 | 379.5 ± 202.6 | 324.2 ± 122.9 | 495.7 ± 480.7 | ||||
| Median | 339.6 | 294.8 | 270.6 | 364.7 | ||||
| Minimum, maximum | 244.6, 538.1 | 179.9, 698.2 | 187.4, 591.2 | 171.8, 1661.9 | ||||
AUC area under the plasma concentration–time curve, AUC(0–z) AUC from time zero to the last timepoint, AUC(0–∞) AUC from time zero to infinity, CL/F apparent total clearance of the drug from plasma after oral administration, Cmax maximum plasma drug concentration, N number of participants, SD standard deviation, tmax time to reach maximum (peak) plasma concentration following drug administration, t1/2 apparent terminal elimination half-life, λz apparent terminal disposition rate constant, Vd/F apparent volume of distribution