Table 2.
Summary of primary pharmacokinetic parameters for sacubitril/valsartan analytes
| Analyte | PK parameter | Treatment | Mean ± SD | CV (%) | Adjusted geometric meana | GMRa (90% CI) | Intrasubject CV (%) |
|---|---|---|---|---|---|---|---|
| Sacubitril | AUCtau,ss (h*ng/mL) | Sacubitril/valsartan + Sildenafil | 3700 ± 912 | 24.6 | 3592 | 1.10 (1.04, 1.17) | 12.2 |
| Sacubitril/valsartan alone | 3400 ± 1000 | 29.6 | 3259 | ||||
|
Cmax,ss
(ng/mL) |
Sacubitril/valsartan + Sildenafil | 2310 ± 1020 | 44.3 | 2084 | 0.90 (0.74, 1.10) | 45.3 | |
| Sacubitril/valsartan alone | 2470 ± 865 | 35.0 | 2314 | ||||
| Sacubitrilat | AUCtau,ss (h*ng/mL) | Sacubitril/valsartan + Sildenafil | 147000 ± 31000 | 21.0 | 144058 | 1.02 (1.01, 1.04) | 3.7 |
| Sacubitril/valsartan alone | 143000 ± 26300 | 18.4 | 140803 | ||||
|
Cmax,ss
(ng/mL) |
Sacubitril/valsartan + Sildenafil | 14000 ± 2420 | 17.3 | 13812 | 0.94 (0.88, 0.99) | 13.0 | |
| Sacubitril/valsartan alone | 14900 ± 2250 | 15.1 | 14762 | ||||
| Valsartan | AUCtau,ss (h*ng/mL) | Sacubitril/valsartan + Sildenafil | 23600 ± 9500 | 40.3 | 21692 | 0.71 (0.62, 0.80) | 28.0 |
| Sacubitril/valsartan alone | 33000 ± 12400 | 37.5 | 30758 | ||||
|
Cmax,ss
(ng/mL) |
Sacubitril/valsartan + Sildenafil | 3350 ± 1480 | 44.0 | 3044 | 0.61 (0.53, 0.71) | 32.6 | |
| Sacubitril/valsartan alone | 5300 ± 1750 | 33.0 | 4994 |
N = 27, unless otherwise mentioned. AUCtau,ss, area under plasma concentration‐time curve from time zero to the end of dosing interval τ (tau) at steady state; CI, confidence interval; Cmax, maximum plasma concentration; Cmax,ss, maximum plasma concentration following drug administration at steady state; CV%, coefficient of variation (%); GMR, geometric mean ratio; PK, pharmacokinetic; SD, standard deviation.
Back‐transformed from log scale. Log‐transformed pharmacokinetic parameter data were analyzed using a fixed effect model with subject and treatment (sacubitril/valsartan + sildenafil vs. sildenafil alone) as fixed effects.