Table 2.
Final tapentadol population pharmacokinetics parameter estimates and 95% confidence intervals. Estimates of CL/F and V/F relate to a reference weight of 45 kg
| Parameter | Estimate | RSE (%) | 95% Confidence interval | |
|---|---|---|---|---|
| NONMEM | Bootstrap (n=500) | |||
| CL/F (L/h) | 170 | 3.3 | 159.06–180.94 | 162.08–182.94 |
| V/F (L) | 685 | 4.5 | 624.83–745.17 | 653.55–777.96 |
| Ka (h−1) | 2.03 | 16.5 | 1.373–2.687 | 1.599–3.263 |
| TLAG (h) | 0.247 | 0.7 | 0.243–0.251 | 0.245–0.273 |
| Exponent CL-WT | 0.638 | 11.1 | 0.499–0.777 | 0.515–0.766 |
| Exponent V-WT | 0.847 | 10.2 | 0.678–1.016 | 0.718–1.029 |
| Additive error (ng/mL) | 0.181 | 39.1 | 0.042–0.32 | 0.036–0.415 |
| Proportional error (σ) | 0.329 | 8.7 | 0.273–0.385 | 0.269–0.365 |
| IIV CL/F (ω2) | 0.048 | 32.1 | 0.018–0.078 | 0.025–0.088 |
| IIV V/F (ω2) | 0.024 | 61.5 | −0.005–0.053 | 0.012–0.081 |
| IIV Ka (ω2) | 1.99 | 32.2 | 0.734–3.246 | 1.042–3.673 |
| Cov CL/F-V/F | 0.03 | 46.1 | 0.003–0.057 | 0.012–0.071 |
| Cov CL/F-Ka | 0.009 | 614.5 | −0.107–0.126 | −0.090–0.155 |
| Cov V/F-Ka | −0.072 | 93.6 | −0.203–0.060 | −0.219–0.080 |
Abbreviations: CL/F, apparent clearance after OS administration; Cov, covariance; σ, standard deviation; ω2, variance; IIV, inter-individual variability; Ka, first-order absorption rate constant; RSE, relative standard error (derived from the covariance matrix of the estimates reported by NONMEM); TLAG, absorption lag-time; V/F, apparent volume of distribution after OS administration; WT, weight.