Table 3.
Pharmacokinetic parameters of sildenafil and UK-103,320 in normal subjects and those with hepatic impairment after administration of single 50-mg sildenafil dose. Geometric mean±SDs are presented for Cmax, AUC and CL/F; arithmetic mean±SDs are presented for kel and fraction unbound; median plus range are presented for Tmax; and harmonic means are presented for t1/2.
| Parameter | Normal | Cirrhotic |
|---|---|---|
| Sildenafil | ||
| Cmax (ng ml−1) | 155±56 | 228±131 |
| Ratio (/normal) | – | 1.47 |
| 95% CI | – | 0.97, 2.22 |
| P-value | – | 0.0667 |
| AUC (ng ml−1 h) | 664±254 | 1225±296 |
| Ratio (/normal) | – | 1.85 |
| 95% CI | – | 1.11, 3.07 |
| P-value | – | 0.0227 |
| Tmax (h) | 1.5 [1.0–2.0] | 1.5 [1.0–2.0] |
| kel (h−1) | 0.215±0.059 | 0.163±0.051 |
| Fraction unbound (%) | 3.46±0.61 | 3.70±1.34 |
| CL/F (ml min−1) | 1255±533 | 680±712 |
| t1/2 (h) | 3.2 | 4.3 |
| UK-103,320 | ||
| Cmax (ng ml−1) | 83±38 | 155±51 |
| Ratio (/normal) | – | 1.87 |
| 95% CI | – | 1.31, 2.68 |
| P-value | – | 0.0026 |
| AUC (ng ml−1 h) | 343±162 | 873±343 |
| Ratio (/normal) | – | 2.54 |
| 95% CI | – | 1.68, 3.85 |
| P-value | – | 0.0004 |
| Tmax (h) | 1.0 [1.0–2.0] | 1.5 [1.0–2.0] |
| kel (h−1) | 0.223±0.101 | 0.120±0.048 |
| Fraction unbound (%) | 4.86±1.01 | 5.55±1.45 |
| t1/2 (h) | 3.1 | 5.8 |