Table 2.
Effect of saquinavir and ritonavir on the pharmacokinetics of single‐dose sildenafil.
| Pharmacokinetic parameter | |||||
|---|---|---|---|---|---|
| Treatment regimen | AUC† (ng ml−1 h) | Cmax† (ng ml−1) | tmax‡ (h) | λz‡ (h−1) | |
| Study I(n = 27) | |||||
| Saquinavir | |||||
| Sildenafil (day 1) | 1378 | 296 | 2.1 | 0.207 | |
| Sildenafil (day 7/8)/saquinavir (day 2–8) | 4261 | 609 | 4.8 | 0.156 | |
| Placebo | |||||
| Sildenafil (day 1) | 1468 | 302 | 3.1 | 0.199 | |
| Sildenafil (day 7/8)/placebo (day 2–8) | 1459 | 256 | 3.3 | 0.194 | |
| *P value | < 0.0001 | < 0.0001 | 0.0012 | 0.012 | |
| Study II(n = 28) | |||||
| Ritonavir | |||||
| Sildenafil (day 1) | 1419 | 321 | 2.0 | 0.183 | |
| Sildenafil (day 7/8)/ritonavir (day 2–8) | 13278 | 1063 | 5.6 | 0.127 | |
| Placebo | |||||
| Sildenafil (day 1) | 1502 | 325 | 2.3 | 0.193 | |
| Sildenafil (day 7/8)/placebo (day 2–8) | 1342 | 274 | 2.7 | 0.198 | |
| *P value | < 0.0001 | < 0.0001 | 0.0018 | 0.0003 | |
Sildenafil administered as a single 100 mg dose; saquinavir administered at a dosage of 1200 mg three times daily; ritonavir administered at a dosage of 300, 400 and 500 mg twice daily on days 2, 3 and 4–8, respectively.
*
intergroup comparison (saquinavir/ritonavir vs placebo) of change in sildenafil pharmacokinetics from day 1 to day 7/8
†
geometric mean
‡
arithmetic mean.