TABLE 3.
Parameter estimates for the final population pharmacokinetic model
| Parameter | Estimate | ASE | % RSE | 95% CI | Units |
|---|---|---|---|---|---|
| CL/F | 80.7 | 20.2 | 25.0 | (41.1–120) | L/h |
| V 2/F | 438 | 36.7 | 8.39 | (366–510) | L |
| V 3/F | 1.42 | 0.49 | 34.2 | (0.468–2.38) | L |
| k a for sublingual administration | 6.58 | 1.06 | 16.2 | (4.49–8.67) | h–1 |
| k a for subcutaneous administration | 17.6 | 1.48 | 8.40 | (14.7–20.5) | h–1 |
| k30 | 1.28 | 0.494 | 38.5 | (0.32–2.25) | h–1 |
| k a for apomorphine sulfate absorption from the gastrointestinal tract | 0.205 | 0.180 | 87.9 | (−0.15 to 0.55) | h–1 |
| Fraction not swallowed and available for sublingual absorption | 0.910 | 0.0533 | 5.86 | (0.805–1.01) | |
| Fraction absorbed relative to subcutaneous administration | 0.202 | 0.0258 | 12.8 | (0.152–0.253) | |
| k26 | 0.613 | 0.0859 | 14.0 | (0.445–0.781) | h–1 |
| k62 | 0.00480 | 0.000762 | 15.9 | (0.00330–0.00630) | h–1 |
| Dose of sublingual apomorphine on F 1 | −0.206 | 0.339 | 165 | (−0.870 to 0.459) | |
| Contact time under the tongue for sublingual film on k a for sublingual administration | –0.194 | 0.119 | 61.5 | (–0.428 to –0.0400) | |
| Body weight on V 2/F | 1.53 | 0.379 | 24.8 | (0.788–2.27) | |
| Study CTH−103 on V 2/F | −0.555 | 0.0476 | 8.59 | (–0.648 to −0.462) | |
| Female sex on V 3/F | –0.310 | 0.0663 | 21.4 | (–0.440 to –0.180) | |
| Residual variability | |||||
| Apomorphine | 44.3 | 1.45 | 3.26 | (41.5–47.2) | % |
| Apomorphine sulfate | 58.0 | 2.21 | 3.81 | (53.6–62.3) | % |
| Interindividual variability | |||||
| k23 | 35.9 | (16.6–47.9) | %CV | ||
| V 2/F | 41.7 | (27.5–52.1) | %CV | ||
| V 3/F | 40.3 | (27.9–49.7) | %CV | ||
| k a for sublingual administration | 35.7 | (24.7–41.1) | %CV | ||
| F 1 | 38.3 | (27.2–46.7) | %CV | ||
Abbreviations: % RSE, percent relative standard error; %CV, percent coefficient of variation; ASE, asymptotic standard error; CI, confidence interval; CL/F, apparent apomorphine clearance; F 1, bioavailability of apomorphine sublingual film; k23, first‐order rate constant for the metabolism of apomorphine to apomorphine sulfate and equal to CL/V 2; k26, distribution rate constant for apomorphine moving from central to tissue compartment; k30, elimination rate constant for apomorphine sulfate; k62, distribution rate constant for apomorphine moving from tissue to central compartment; k a, first‐order absorption rate constant; V 2/F, apparent volume of distribution for apomorphine; V 3/F, apparent volume of distribution for apomorphine sulfate.