Table 4.
Bioavailability and pharmacokinetic comparisons between doses received population: PK analysis.
| Low-dose sublingual/high-dose sublingual | Low-dose sublingual/intravenous | High dose sublingual/intravenous | |
|---|---|---|---|
| Parameter statistic | |||
| AUC∞ (min*ng/mL) | |||
| Ratio | |||
| Geometric mean | 0.579 | 0.349 | 0.603 |
| 90% CI | (0.526, 0.636) | (0.317, 0.384) | (0.552, 0.658) |
| Dose corrected ratio | |||
| Geometric Mean | 1.157 | 0.698 | NA |
| 90% CI | (1.053, 1.272) | (0.634, 0.768) | |
| AUCt (min*ng/mL) | |||
| Ratio | |||
| Geometric mean | 0.546 | 0.306 | 0.561 |
| 90% CI | (0.497, 0.600) | (0.279, 0.337) | (0.510, 0.616) |
| Dose corrected ratio | |||
| Geometric mean | 1.093 | 0.613 | NA |
| 90% CI | (0.994, 1.201) | (0.558, 0.673) | |
| Cmax (ng/mL) | |||
| Ratio | |||
| Geometric mean | 0.549 | 0.049 | 0.090 |
| 90% CI | (0.424, 0.712) | (0.038, 0.064) | (0.069, 0.117) |
| Dose corrected ratio | |||
| Geometric mean | 1.098 | 0.099 | NA |
| 90% CI | (0.847, 1.424) | (0.076, 0.128) | |
| AUC45 (min*ng/mL) | |||
| Ratio | |||
| Geometric mean | 0.635 | 0.031 | 0.049 |
| 90% CI | (0.432, 0.931) | (0.021, 0.045) | (0.033, 0.072) |
| Dose corrected ratio | |||
| Geometric mean | 1.269 | 0.062 | NA |
| 90% CI | (0.865, 1.862) | (0.042, 0.091) | |
| AUC60 (min*ng/mL) | |||
| Ratio | |||
| Geometric mean | 0.558 | 0.045 | 0.081 |
| 90% CI | (0.380, 0.821) | (0.031, 0.066) | (0.055, 0.119) |
| Dose corrected ratio | |||
| Geometric Mean | 1.117 | 0.090 | NA |
| 90% CI | (0.759, 1.643) | (0.061, 0.132) | |
| AUC120 (min*ng/mL) | |||
| Ratio | |||
| Geometric mean | 0.499 | 0.121 | 0.242 |
| 90% CI | (0.393, 0.634) | (0.095, 0.153) | (0.190, 0.307) |
| Dose corrected ratio | |||
| Geometric mean | 0.998 | 0.241 | NA |
| 90% CI | (0.786, 1.267) | (0.190, 0.307) | |
| AUC240 (min*ng/mL) | |||
| Ratio | |||
| Geometric mean | 0.529 | 0.233 | 0.440 |
| 90% CI | (0.462, 0.605) | (0.203, 0.266) | (0.385, 0.504) |
| Dose corrected ratio | |||
| Geometric mean | 1.058 | 0.466 | NA |
| 90% CI | (0.924, 1.210) | (0.407, 0.533) |
AUC∞, area under curve to infinity; AUCt, AUC to last quantifiable data point; AUC45, AUC to 45-min timepoint; AUC60, AUC to 60-min timepoint; AUC120, AUC to 120-min timepoint; AUC240, AUC to 240-min timepoint; CI, confidence interval; Cmax, maximum concentration; NA, not applicable; PK, pharmacokinetic
Note: Only subjects who had at least 2 periods where study drug was received with an evaluable PK profile were included in the comparisons. All statistics are back-transformed and based on a random effects linear model with log10 numeric response variable, adjusting for study dosage received, dosing sequence, and period, with a random effect for subject nested within dosing sequence
Note: Dose corrected ratios do not apply to the ratio of high-dose sublingual to intravenous due to the doses being equivalent