Table 3.
Statistical assessment of ethnic differences of pharmacokinetic parameters in fidaxomicin (200 mg) and its metabolite OP-1118
| Compound | Dose schedule | Pharmacokinetic parameter | Japanese (Test) | Caucasian (reference) | Geometric LS mean ratio (test/reference)a | 90 % CI for the ratio | ||
|---|---|---|---|---|---|---|---|---|
| n | Geometric LS mean | n | Geometric LS mean | |||||
| Fidaxomicin | Single dose | AUC∞ (ng·h/mL) | 7 | 50.06 | 8 | 50.70 | 0.99 | 0.61–1.60 |
| AUClast (ng·h/mL) | 9 | 51.69 | 8 | 40.32 | 1.28 | 0.79–2.09 | ||
| C max (ng/mL) | 9 | 7.28 | 8 | 4.29 | 1.70 | 1.05–2.75 | ||
| Multiple dose | AUCτ (ng·h/mL) | 8 | 49.36 | 9 | 34.76 | 1.42 | 0.91–2.23 | |
| C max,ss (ng/mL) | 8 | 7.42 | 9 | 6.11 | 1.21 | 0.74–2.00 | ||
| OP-1118 | Single dose | AUC∞ (ng·h/mL) | 7 | 148.03 | 8 | 123.24 | 1.20 | 0.90–1.61 |
| AUClast (ng·h/mL) | 9 | 146.91 | 8 | 112.52 | 1.31 | 0.95–1.80 | ||
| C max (ng/mL) | 9 | 16.92 | 8 | 10.45 | 1.62 | 1.16–2.27 | ||
| Multiple dose | AUCτ (ng·h/mL) | 8 | 127.91 | 9 | 84.85 | 1.51 | 1.08–2.11 | |
| C max,ss (ng/mL) | 8 | 18.10 | 9 | 13.79 | 1.31 | 0.92–1.87 | ||
A one-way ANOVA was utilized to analyze the effect of ethnic group differences (Japanese vs. Caucasian) on pharmacokinetic response. Pharmacokinetic parameters were analyzed on the logarithmic scale
ANOVA analysis of variance, AUC area under the concentration–time curve, AUC ∞ AUC from time zero to infinity, AUC last AUC from time zero to time of last measurable concentration, AUC τ AUC over the dosing interval at steady state, CI confidence interval, C max maximum plasma concentration, C max,ss C max at steady state, LS least squares
aRatio of log-transformed pharmacokinetic parameters between Japanese and Caucasian subjects and its 90 % CI are back-transformed to the raw scale