Table 4.
Parameter estimates (s.e. estimate) and objective function values for the pharmacodynamic modela
| Parameter | Healthy volunteers | Patients – no covariates | Patients – full model | Patients – final model |
|---|---|---|---|---|
| Structural model parameters (θ : s) | ||||
| APTTbaseline (θ1) | 35.1 (0.5) | 29.5 (0.1) | 29.2b (0.1) | 29.2b (0.1) |
| RefLow on APTTbaseline (θ5) | – | – | 0.36b (0.06) | 0.36b (0.06) |
| Age on APTTbaseline (θ6) | – | – | −0.039b (0.019) | – |
| SLOPE (θ2) | 8.0 (0.6) | 5.8 (1.4) | 5.6 (1.4) | 5.8 (1.4) |
| Emax (θ3) | 36 (2) | 31 (5) | 32c (5) | 31c (5) |
| RefLow on Emax (θ7) | – | – | 0.70c (0.23) | 0.67c (0.22) |
| Diagnosis on Emax (θ8) | – | – | −2.8c (1.2) | – |
| EC50 (θ4) | 0.54 (0.06) | 0.72 (0.12) | 0.74 (0.11) | 0.72 (0.12) |
| Interindividual variability parameters (ω : s) | ||||
| APTTbaseline (%) | 10 (2) | 12 (2) | 11 (2) | 11 (2) |
| Emax (%) | 20 (4) | 29 (8) | 28 (8) | 28 (8) |
| Correlation between APTTbaseline and Emax (r) | 1.00 (17%)d | 0.43 (39%)d | 0.37 (49%)d | 0.37 (49%)d |
| Interoccasion variability parameter (π) | ||||
| APTTbaseline (%) | 4.5 (1.1) | N.A. | N.A | N.A. |
| Residual error parameter (σ) | ||||
| Coefficient of variation (%) | 5.0 (1.0) | 8.9 (0.9) | 8.8 (0.9) | 8.8 (0.9) |
| Objective function value | 3371 | 9298 | 9222 | 9237 |
a
APTT=APTTbaseline+SLOPE C +Emax C/(EC50 + C), where C is the concentration in µmol l−1 and APTT is in s.
b
APTTbaseline=θ1 + θ5 (RefLow - 25)−θ6(Age-66), where 25 is the median of the lower limit of the reference range for the APTT method and 66 is the median age.
c
Emax=θ3 + θ7 (RefLow - 25) + θ8Diagnosis, where 0=Angina pectoris and 1 = Non-Q-wave myocardial infarction.
d
Relative s.e. of COV(APTTbaseline, Emax)