Table 2.
Summary of pharmacodynamic parameters for xanthine
| Xanthine |
Cmean,24 (mg/dL)
|
Change in Cmean,24 (%)
|
CLR (mL/min)
|
|||||
|---|---|---|---|---|---|---|---|---|
| Baseline | Day 1 (Day 8*) |
Day 7 | Day 1 (Day 8*) |
Day 7 | Baseline | Day 1 (Day 8*) |
Day 7 | |
| SAD study | ||||||||
| 10 mg (n=6) | 0.028 (0.011) | 0.074 (0.006) | – | 206.9 (132.6) | – | 28.9 (19.4) | 65.1 (14.3) | – |
| 25 mg (n=6) | 0.031 (0.009) | 0.094 (0.010) | – | 225.6 (123.9) | – | 16.6 (6.7) | 63.7 (5.0) | – |
| 50 mg (n=8) | 0.024 (0.005) | 0.114 (0.008) | – | 385.0 (87.9) | – | 24.6 (7.6) | 64.8 (7.2) | – |
| 100 mg (n=8) | 0.030 (0.006) | 0.139 (0.015) | – | 366.9 (69.5) | – | 14.6 (4.5) | 67.0 (12.6) | – |
| 200 mg (n=8) (fasting) | 0.021 (0.003) | 0.162 (0.016) | – | 697.6 (174.3) | – | 26.8 (4.3) | 75.4 (14.5) | – |
| 200 mg (n=8) (fed)* | – | 0.141 (0.015) | 590.8 (132.9) | – | 73.7 (22.1) | |||
| 400 mg (n=8) | 0.038 (0.006) | 0.224 (0.029) | – | 503.7 (16.4.3) | – | 15.7 (4.5) | 78.5 (19.5) | – |
| 600 mg (n=8) | 0.035 (0.014) | 0.197 (0.022) | – | 541.7 (216.3) | – | 17.0 (10.5) | 70.7 (20.9) | – |
| Placebo (n=14) | 0.028 (0.007) | 0.031 (0.010) | – | 8.7 (23.1) | – | 21.7 (8.6) | 20.4 (10.5) | – |
| MAD study | ||||||||
| 100 mg (n=8) | 0.036 (0.003) | 0.138 (0.015) | 0.156 (0.019) | 291.9 (58.0) | 344.1 (79.9) | 15.1 (4.0) | 61.8 (8.5) | 57.0 (8.0) |
| 200 mg (n=8) | 0.044 (0.009) | 0.169 (0.026) | 0.221 (0.027) | 289.4 (63.8) | 418.1 (126.9) | 12.9 (3.5) | 78.8 (17.2) | 82.1 (14.0) |
| 400 mg (n=8) | 0.036 (0.007) | 0.192 (0.035) | 0.249 (0.050) | 450.6 (166.0) | 611.3 (203.9) | 15.3 (5.8) | 66.0 (15.8) | 70.8 (15.5) |
| 600 mg (n=8) | 0.045 (0.026) | 0.195 (0.032) | 0.262 (0.054) | 419.1 (213.2) | 617.2 (340.1) | 12.4 (6.2) | 62.3 (23.0) | 66.4 (16.5) |
| 800 mg (n=6) | 0.032 (0.008) | 0.185 (0.023) | 0.295 (0.057) | 495.0 (130.8) | 846.7 (246.6) | 11.6 (5.5) | 68.7 (14.3) | 74.7 (14.3) |
| Febuxostat 80 mg (n=8) | 0.042 (0.009) | 0.182 (0.036) | 0.235 (0.067) | 333.8 (60.4) | 454.5 (92.3) | 10.9 (4.2) | 55.7 (16.6) | 59.6 (12.7) |
| Placebo (n=10) | 0.036 (0.008) | 0.033 (0.009) | 0.035 (0.007) | −8.3 (15.1) | −1.1 (16.3) | 13.6 (4.7) | 15.8 (6.8) | 14.2 (4.2) |
Notes: All values are presented as mean (SD).
*
Data of 200 mg dose group under fed condition.
Abbreviations: Cmean,24, 24-hour mean serum concentrations of xanthine; CLR, renal clearance of xanthine; min, minutes; SAD, single ascending dose; MAD, multiple ascending dose; SD, standard deviation.