Table 3.
Population PD estimates and interaction term (ALPHA) of amlodipine and valsartan combined administration in healthy subjects
| SBP | |||
|---|---|---|---|
| Interaction type | Proportional | ||
| No. of parameters | 8 | ||
| Parameter | Estimate (RSE%) | Bootstrap estimate | 95% CI |
| BSL (mmHg) | 117 (1.10) | 116.8 | 114–119.0 |
| ALPHA | −0.171 (11.6) | −0.178 | −0.218–−0.143 |
| PPV | Estimate (RSE%) | Bootstrap estimate | 95% CI |
| BSL | 0.059 (18.8) | 0.055 | 0.035–0.074 |
| ALPHA | 0 FIX | ||
| IC 501 | 0.468 (84.3) | 0.341 | 0–0.872 |
| IC 502 | 1.732 (43.4) | 1.671 | 0–3.127 |
| AML Keq a | 1.319 (46.5) | 1.336 | 0–2.403 |
| VAL Keq a | 0.376 (37.9) | 0.371 | 0–0.613 |
| Residual variability | Estimate (RSE%) | Bootstrap estimate | 95% CI |
| σ additive (mmHg) | 7.84 (6.36) | 7.84 | 6.86–8.73 |
| DBP | |||
|---|---|---|---|
| Interaction type | Proportional | ||
| No. of parameters | 6 | ||
| Parameter | Estimate (RSE%) | Bootstrap estimate | 95% CI |
| BSL (mmHg) | 72.8 (1.33) | 72.9 | 71.2–74.7 |
| ALPHA | −0.0312 (57.8) | −0.0336 | −0.0774–−0.00283 |
| PPV | Estimate (RSE%) | Bootstrap estimate | 95% CI |
| BSL | 0.071 (15.9) | 0.07 | 0.046–0.092 |
| ALPHA | 0 FIX | ||
| ω IC 501 | 1.612 (33.1) | 1.674 | 0.907–2.819 |
| ω IC 502 | 1.131 (32.8) | 1.042 | 0.004–1.622 |
| Residual variability | Estimate (RSE%) | Bootstrap estimate | 95% CI |
| σ additive (mmHg) | 4.46 (5.22) | 4.45 | 3.95–4.90 |
ALPHA, interaction term for co‐administration of amlodipine and valsartan; BSL, estimated baseline; other parameters (I max, etc.) fixed to values estimated from combined administration PK models and single drug PD models. PPV value calculated from sqrt(NONMEM OMEGA estimate)