Table 2.
Pharmacokinetic parameters for fidaxomicin and its metabolite OP-1118
| Compound | Pharmacokinetic parameter | Japanese 100 mg single dose | Japanese 200 mg single dose | Caucasian 200 mg single dose | Japanese 100 mg multiple dose | Japanese 200 mg multiple dose | Caucasian 200 mg multiple dose | |
|---|---|---|---|---|---|---|---|---|
| Fidaxomicin | C max (ng/mL) | n | 9 | 9 | 9 | 9 | 8 | 9 |
| Mean ± SD | 4.5 ± 2.4 | 8.3 ± 4.5 | 4.5 ± 3.4 | 5.3 ± 2.9 | 8.7 ± 5.3 | 7.0 ± 3.7 | ||
| AUCa (ng·h/mL) | n | 8 | 7 | 8 | 9 | 8 | 9 | |
| Mean ± SD | 40.6 ± 15.8 | 55.6 ± 26.4 | 57.5 ± 30.0 | 32.8 ± 20.5 | 58.5 ± 36.7 | 37.6 ± 15.7 | ||
| t ½ (h) | n | 8 | 7 | 8 | 5 | 6 | 7 | |
| Mean ± SD | 7.0 ± 3.5 | 10.6 ± 8.1 | 13.9 ± 5.8 | 11.7 ± 6.1 | 7.8 ± 1.8 | 13.9 ± 3.5 | ||
| CL/F (L/h) | n | 8 | 7 | 8 | 9 | 8 | 9 | |
| Mean ± SD | 2791 ± 964 | 4464 ± 2291 | 4459 ± 2288 | 3877 ± 1699 | 4734 ± 2636 | 6265 ± 2896 | ||
| t max (h) | n | 9 | 9 | 8 | 9 | 8 | 9 | |
| Median | 3.00 | 2.00 | 2.00 | 2.00 | 3.00 | 4.00 | ||
| Min–Max | 1.00–4.07 | 1.00–6.00 | 1.00–4.00 | 1.00–6.00 | 1.00–8.00 | 1.00–4.00 | ||
| R acc | n | NA | NA | NA | 9 | 8 | 8 | |
| Mean ± SD | NA | NA | NA | 1.30 ± 0.44 | 1.37 ± 0.48 | 1.61 ± 0.79 | ||
| OP-1118 | C max (ng/mL) | n | 9 | 9 | 9 | 9 | 8 | 9 |
| Mean ± SD | 8.6 ± 4.0 | 18.0 ± 7.6 | 10.1 ± 5.9 | 10.2 ± 4.8 | 19.8 ± 8.9 | 14.7 ± 5.5 | ||
| AUCa (ng·h/mL) | n | 8 | 7 | 8 | 9 | 8 | 9 | |
| Mean ± SD | 92.7 ± 40.3 | 154.2 ± 48.5 | 129.9 ± 49.6 | 67.6 ± 31.9 | 144.2 ± 74.9 | 86.8 ± 18.9 | ||
| t ½ (h) | n | 8 | 7 | 8 | 8 | 6 | 9 | |
| Mean ± SD | 8.8 ± 3.1 | 11.5 ± 7.6 | 16.7 ± 7.0 | 10.4 ± 4.6 | 8.3 ± 1.5 | 13.7 ± 6.3 | ||
| t max (h) | n | 9 | 9 | 8 | 9 | 8 | 9 | |
| Median | 3.00 | 3.00 | 2.00 | 2.00 | 3.00 | 3.00 | ||
| Min–Max | 1.00–6.00 | 1.00–6.00 | 1.00–4.00 | 1.00–6.00 | 1.00–8.00 | 1.00–4.00 | ||
| R acc | n | NA | NA | NA | 9 | 8 | 8 | |
| Mean ± SD | NA | NA | NA | 1.26 ± 0.33 | 1.37 ± 0.50 | 1.67 ± 0.71 | ||
AUC area under the concentration–time curve, AUC ∞ AUC from time zero to infinity, AUC 12 AUC from time zero to 12 h, CL/F apparent total clearance, C max maximum plasma concentration, min minimum, max maximum, NA not analyzed, R acc accumulation ratio, SD standard deviation, t ½ terminal elimination half-life, t max time to C max
aSingle dose: AUC∞, multiple dose: AUC12