Table 2.
Population estimates for pharmacokinetic and pharmacodynamic models for scopolamine
| CL [α] ( l min −1 ) | IIV (shrinkage) | V c (l) | IIV (shrinkage) | V p [β] (l) | IIV (shrinkage) | Q ( min −1 ) | CAC | CWC | CWV | Error (σ 2 ) | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Scopolamine pharmacokinetics | 1.09 ± 0.096* , † | 10.3% (9.7) | 2.66 ± 1.050 | 74.1% (49.3) | 62.10 ± 10.100† | 9.5% (25.6) | 1.01 ± 0.247 | −0.12 ± 0.019 | 0.56 ± 0.097 | 0.38 ± 0.120 | 0.045 (prop) |
| EC 50 [ε] (pg ml−1) | IIV (shrinkage) | E MAX (%) | IIV (shrinkage) | K IN [λ] | IIV (shrinkage) | K OUT | CAB or CAE | γ‡ | OC | Error (σ2) | |
| 0‐back RT (msec) | 1300 ± 363 | 99.8% (33.2) | 0.837 ± 0.118 | NA | 3.42 ± 0.361* | 10.5% (8.13) | 0.00974 ± 0.00099 | 229 ± 40.9 | NA | NA | 0.00999 (prop) |
| Saccadic inaccuracy (%) | 55.1 ± 29.8 | 13.7% (36.9)¶ | 0.388 ± 0.079 | 49.9% (36.2)¶ | 22.8 ± 0.731 | 13.2% (21.86) | 3.33 ± 0.0398 | NA | NA | −0.06 ± 0.157 | 0.0493 (prop) |
| Saccadic peak velocity (deg sec−1) | 2530 ± 213* | 277.0% (20.9) | 0.232 ± 0.00113 | NA | 1280 ± 21 | 9.9% (3.1) | 2.73 ± 0.0468 | 34.0 ± 1.39 | NA | NA | 768.0 (prop) |
| Adaptive tracker (%) | 386 ± 22.6 | 85.5% (10.50) | 1 | NA | 0.636 ± 0.0413 | 22.4% (4.1) | 0.0294 ± 0.0018 | NA | 1.10 ± 0.063 | NA | 8.64 (add) |
| EEG alpha Fz‐Cz (μV) | 2.55 ± 1.06 | 1530.0% (48.4) | 0.232 ± 0.0258 | 95.4% (14.9) | 0.206 ± 0.0344 | 46.6% (1.1) | 0.0699 ± 0.0113 | NA | NA | NA | 0.0256 (prop) |
| EEG alpha Pz‐Oz (μV) | 14.7 ± 0.168 | 1309.3% (27.9) | 0.443 ± 0.00389 | 37.6% (18.0) | 3.05 ± 0.135 | 57.9% (2.1) | 0.553 ± 0.0055 | NA | NA | NA | 0.0429 (prop) |
| EEG delta Fz‐Cz (μV) | 469 ± 70.8 | 154.5% (35.5)¶ | 0.419 ± 0.0515 | 325.4% (19.2)¶ | 0.0354 ± 0.00369* | 28.9% (2.1)¶ | 0.0166 ± 0.00161 | 161 ± 30 | NA | 1.410 ± 0.722 (EC 50 vs. E MAX); −0.153 ± 0.0494 (E MAX vs. k in) | 0.0338 (prop) |
| EEG delta Pz‐Oz (μV) | 1230 ± 368 | 1166.2% (29.6) | 0.537 ± 0.0601 | 55.8% (48.0) | 0.726 ± 0.186* | 30.3% (1.7) | 0.348 ± 0.084 | 210 ± 63.7 | NA | NA | 0.0304 (prop) |
| EEG theta Fz‐Cz (μV) | 4110 ± 1410 | 2162.7% (31.1) | 0.594 ± 0.106 | NA | 0.863 ± 0.0422* | 28.4% (1.8) | 0.594 ± 0.106 | 142 ± 24.7 | NA | NA | 0.0297 (prop) |
| EEG theta Pz‐Oz (μV) | 8240 ± 6270 | 1778.6% (27.9) | 1.15 ± 0.179 | NA | 13 ± 8.79 | 33.4% (0.5) | 6.08 ± 4.23 | NA | NA | NA | 0.0379 (prop) |
| EC 50 (pg ml−1) | K IN | IIV (shrinkage) | K OUT | E MAX (%) | IIV (shrinkage) | E 0 | IIV (shrinkage) | NA | OC | Error (σ2) | |
| 0‐back ratio (% correct answers) ** | 2140 ± 1720 | 0.0354 ± 0.00244§ | NA | 0.036 ± 0.0061 | 1 | 631.3% (42.1)¶ | 3.77 ± 0.274 | 37.8% (20.1)¶ | NA | 0.40 ± 0.141 | 0.0039 (add) |
| 1‐back ratio (% correct answers) ** | 0.624 ± 0.0053 | 1.10 ± 0.0175 | 578.5% (47.3) | 221 ± 4.35 | 0.961 ± 0.00511 | 121.6% (30.0) | 3.33 ± 0.0293 | NA | NA | NA | 0.0059 (add) |
| 2‐back ratio (% correct answers) ** | 212 ± 72.4 | 0.54 ± 0.103 | NA | 0.317 ± 0.0704 | 1.09 ± 0.248 | 109.8% (31.9)¶ | 2.84 ± 0.164 | 35.9% (21.5)¶ | NA | 0.23 ± 0.107 | 0.0085 (add) |
Parameters are reported as population estimate ± standard error. IIV: Inter‐individual variability expressed as coefficient of variation and shrinkage in parentheses. Baseline is calculated as the ratio of K in and K out.
Age used as a covariate (ε and λ in Equation B.1 of the Supplemental Materials section).
Weight used as covariate.
Exponent in EMAX (γ).
Four buffer compartments.
Omega block structure.
Parameters reported as natural log odds. Prop: proportional error. CAC: coefficient relating age and clearance. CWC: coefficient relating age and weight. CWV: coefficient relating apparent peripheral volume of distribution and weight. CAB: coefficient relating age and K IN. CAE: coefficient relating age and EC 50. OC: correlation between Omegas. E 0: baseline. Add: additive error. NA: not applicable. Please refer to the Supplemental Materials section for the model equations and the parameter‐covariate relationships.