Table II.
Estimates of the population parameters of pharmacodynamic models
| Model and value parameter | Structural model parameters |
Interindividual variability (ω) [%] |
Residual variability (σ) [%] | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| RET0 (%) | TR (h) | Tp (h) | SC50 (IU/L) | Smax | EC50 (IU/L) | τ (h) | RET0 | TR | TP | SC50 | ||
| Model A (n = 927) | ||||||||||||
| Original dataset | 1.29 | 127 | 59.7 | 42.8 | 19.0 | 17.9 | 29.5 | 37.0 | 70.5 | |||
| BS median (RSE %) | 1.29 (2.5) | 127 (4.8) | 59.7 (6.2) | 42.9 (5.7) | 18.7 (11.5) | 17.7 (23.2) | 28.9 (12.4) | 37.0 (12.7) | 70.5 (5.0) | |||
| BS 95% CI | 1.23, 1.36 | 115, 139 | 52.4, 67.1 | 38.2, 47.8 | 14.0. 22.6 | 6.3, 22.8 | 21.7, 36.0 | 26.9, 45.8 | 64.1, 78.0 | |||
| Model B (n = 769) | ||||||||||||
| Original dataset | 1.58 | 96.2 | 165 | 31. 8a | 0.411 | 18.4 | 25.2 | 15.9 | 41. 8a | 69.6 | ||
| BS median (RSE %) | 1.57 (3.4) | 96.5 (16.9) | 166 (11.4) | 32.3 (6.1)a | 0.416 (18.9) | 18.1 (13.8) | 25.5 (50.1) | 15.2 (32.7) | 41.4 (11.4) | 69.4 (5.2) | ||
| BS 95% CI | 1.46, 1.67 | 55.3, 116 | 137, 213 | 28.8, 36.6 | 0.273, 0.588 | 13.2, 22.7 | 0.01, 55.8 | 5.0, 23.6 | 32.4, 50.5a | 63.1, 77.1 | ||
| Model C (n = 702) | ||||||||||||
| Original dataset | 1.51 | 121 | 158 | 15.4/42.2a | 0.806 | 19.9 | 14.5 | 21.3 | 32. 2a | 68.6 | ||
| BS median (RSE %) | 1.51 (2.6) | 119 (7.0) | 160 (6.5) | 15.2 (16.8)/42.4 (10.5)a | 0.819 (22.0) | 19.7 (10.1) | 10.8 (96.6) | 21.3 (12.1) | 32.1 (13.9)a | 68.6 (5.4) | ||
| BS 95% CI | 1.44, 159 | 106, 137 | 139, 179 | 9.5, 20.0/35.6, 52.2a | 0.51, 1.19 | 15.5. 13.2 | <0.01, 21.9 | 16.2, 26.2 | 22.7, 40.1a | 62.3, 76.5 | ||
| Model D (n = 622) | ||||||||||||
| Original dataset | 1.24 | 62.2 | 118 | 7.61a | 56.3 | 4.89 | 19.8 | 36.2 | 27.4 | 107a | 63.1 | |
| BS median (RSE %) | 1.23 (3.23) | 62.2 (8.39) | 117 (13.9) | 7.91 (35.9) | 71.1 (49.5) | 4,83 (60.7) | 19.7 (10.5) | 35.8 (11.5) | 25.1 (23.8) | 108 (18.9)a | 62.9 (4.62) | |
| BS 95% CI | 1.15, 1.30 | 44.1, 78.6 | 86, 144 | 2.81, 14.25a | 34.4, 166.5 | 0.24, 10.8 | 15.6, 23.8 | 27.9, 44.2 | 14.2. 36.5 | 74.1, 154a | 57.5, 68.3 | |
a
SC50P.
τ
= signal transduction transit time; BS = nonparametric bootstrap; EC50 = concentration of recombinant human erythropoietin eliciting 50% of maximum signal; n = number of replicates; RET0 = baseline reticulocyte count; RSE = relative standard error; SC50 = erythropoietin serum concentration necessary to maintain progenitor cell production at 50% of maximum production; SC50P = erythropoietin serum concentration eliciting 50% of maximum stimulation; Smax = maximum stimulation factor; TP = mean lifespan of precursor cells; Tr = mean lifespan of circulating reticulocytes.