TABLE 3.
Platelet parameter estimates using the final structural platelet model (a) and the final platelet model (b)
| (a) Platelet parameter estimates – final structural model | |||||
|---|---|---|---|---|---|
| Description | Parameter (unit) | Estimate | RSE (%) | 95% CI | CV (%) |
| Baseline | BSLN (∙ 109/L) | 257 | – | (244–271) | – |
| Maturation rate | k tr (/h) | 0.0348 | – | (0.0331–0.0366) | – |
| Feedback power term | γ | 0.144 | – | (0.127–0.163) | – |
| Drug effect EC50 | EC50 (μM) | 4.82 | – | (4.22–5.51) | – |
| IIV on baseline | ω2 baseline | 0.125 | 12.4 | (0.0945–0.155) | 35.4 |
| IIV on ktr | ω2 ktr | 0.0167 | 28.2 | (0.00746–0.0259) | 12.9 |
| IIV on γ | ω2 γ | 0.256 | 24.1 | (0.135–0.376) | 50.6 |
| IIV on EC50 | ω2 EC50 | 0.363 | 19.8 | (0.222–0.504) | 60.2 |
| Proportional residual error | σ1 .1 | 0.0765 | 8.2 | (0.0641–0.0889) | – |
| (b) Platelet parameter estimates – final platelet model | |||||
|---|---|---|---|---|---|
| Description | Parameter (unit) | Estimate | RSE (%) | 95% CI | CV (%) |
| Baseline platelets | BSLN (∙ 109/L) | 257 | – | (244, 271) | – |
| Maturation rate | ktr(/h) | 0.0347 | – | (0.0331, 0.0365) | – |
| Feedback power term | γ | 0.157 | – | (0.137, 0.179) | – |
| Drug effect EC50 | EC50 (μM) | 4.85 | – | (4.22, 5.56) | – |
| Feedback GIST | γ GIST | 0.370 | 41.3 | (0.0707, 0.67) | – |
| Feedback NC, prostate | γ NC, prostate | ‐0.306 | 24.7 | (‐0.454, ‐0.158) | – |
| IIV on baseline platelets | ω2 baseline | 0.121 | 12.5 | (0.0914, 0.151) | 34.8 |
| IIV on ktr | ω2 ktr | 0.0171 | 27.6 | (0.00782, 0.0263) | 13.1 |
| IIV on γ | ω2 γ | 0.218 | 24.2 | (0.115, 0.322) | 46.7 |
| IIV on EC50 | ω2 EC50 | 0.383 | 19.5 | (0.237, 0.53) | 61.9 |
| Proportional residual error | σ1.1 | 0.0763 | 8.2 | (0.064, 0.0887) | – |
Abbreviations: γ, feedback power term; CI, confidence interval; CV, coefficient of variation (derived as 100 × √[ω2]); EC50, total active moiety plasma concentration (molibresib + active metabolite composite [GSK3529246]) that provides half the maximal response; GIST, gastrointestinal stromal tumor; IIV, inter‐individual variability; ktr, maturation rate constant; NC, nuclear protein in testis carcinoma; RSE, relative standard error.