Table 1.
Summary of primary pharmacokinetic parameters for sildenafil analytes
| Analyte | PK parameter | Treatment | Mean ± SD | CV (%) | Adjusted geometric meanb | GMRb (90% CI) | Intrasubject CV (%) |
|---|---|---|---|---|---|---|---|
| Sildenafil |
AUCinf
(h*ng/mL) |
Sacubitril/valsartan + Sildenafil | 629 ± 303 | 48.1 | 576 | 1.06 (0.96, 1.19) | 23.4 |
| Sildenafil alone | 601 ± 271 | 45.0 | 541 | ||||
|
AUClast
(h*ng/mL) |
Sacubitril/valsartan + Sildenafil | 612 ± 297 | 48.5 | 559 | 1.06 (0.95, 1.18) | 23.4 | |
| Sildenafil alone | 587 ± 270 | 46.0 | 526 | ||||
|
Cmax
(ng/mL) |
Sacubitril/valsartan + Sildenafil | 189 ± 99.6 | 52.6 | 168 | 1.02 (0.87, 1.19) | 35.5 | |
| Sildenafil alone | 185 ± 88.3 | 47.8 | 165 | ||||
| N‐desmethyl‐sildenafil |
AUCinf
(h*ng/mL) |
Sacubitril/valsartan + Sildenafila | 325 ± 143 | 43.9 | 305 | 0.93 (0.86, 1.00) | 15.9 |
| Sildenafil alonea | 359 ± 157 | 43.9 | 327 | ||||
|
AUClast
(h*ng/mL) |
Sacubitril/valsartan + Sildenafil | 305 ± 133 | 43.5 | 278 | 0.94 (0.87, 1.01) | 16.4 | |
| Sildenafil alone | 331 ± 152 | 46.0 | 297 | ||||
|
Cmax
(ng/mL) |
Sacubitril/valsartan + Sildenafil | 84.6 ± 39.3 | 46.5 | 75.9 | 0.86 (0.76, 0.97) | 26.7 | |
| Sildenafil alone | 95.1 ± 32.5 | 34.2 | 88.4 |
N = 27, unless otherwise mentioned.
AUCinf, area under plasma concentration‐time curve from time zero to infinity; AUClast, area under plasma concentration‐time curve from time zero to the last quantifiable concentration; CI, confidence interval; Cmax, maximum plasma concentration; CV%, coefficient of variation (%); GMR, geometric mean ratio; PK, pharmacokinetic; SD, standard deviation.
N = 26; bBack‐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.