Table 3.
Effect of saquinavir and ritonavir on the pharmacokinetics of the sildenafil metabolite UK‐103,320.
| 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) | 569 | 116 | 2.5 | 0.121 | |
| Sildenafil (day 7/8)/saquinavir (day 2–8) | 1172 | 94 | 6.4 | 0.144 | |
| Placebo | |||||
| Sildenafil (day 1) | 659 | 118 | 3.5 | 0.111 | |
| Sildenafil (day 7/8)/placebo (day 2–8) | 582 | 95 | 3.5 | 0.148 | |
| *P value | < 0.0001 | 0.995 | 0.002 | 0.352 | |
| Study II(n = 28) | |||||
| Ritonavir | |||||
| Sildenafil (day 1) | 567a | 132 | 2.0 | 0.141 | |
| Sildenafil (day 7/8)/ritonavir (day 2–8) | 840a | 55 | 11.7 | na | |
| Placebo | |||||
| Sildenafil (day 1) | 731a | 160 | 2.5 | 0.121 | |
| Sildenafil (day 7/8)/placebo (day 2–8) | 622a | 129 | 2.5 | 0.124 | |
| *P value | < 0.0001 | 0.0002 | 0.0001 | – | |
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.
a
AUC value from time zero to the final quantifiable concentration (AUCt).
*
intergroup comparison (saquinavir/ritonavir vs placebo) of change in UK‐103 320 pharmacokinetics from day 1 to day 7/8
†
geometric mean
‡
arithmetic mean.