Table 2.
Pharmacokinetic parameters for sitaxentan, and sildenafil and N-desmethylsildenafil following administration of sildenafil 100 mg after either sitaxentan 100 mg or placebo for 7 days
| Geometric mean ratio (%)† | ||||
|---|---|---|---|---|
| Parameter* | Sitaxentan 100 mg* | Placebo* | Estimate | 90% CI |
| Sildenafil (n= 22) | ||||
| Cmax (ng ml−1) | 440 ± 232 | 377 ± 208 | 117.61 | 93.81, 147.46 |
| AUC∞ (h ng−1 ml−1) | 1648 ± 692 | 1295 ± 488 | 127.69 | 115.46, 141.22 |
| t1/2 (h) | 2.82 ± 0.45 | 2.76 ± 0.45 | – | – |
| Tmax (h)‡ | 1.25 | 1.00 | – | – |
| AUC0–t (h ng−1 ml−1) | 1575 ± 671 | 1222 ± 474 | 124.95 | 113.40, 137.68 |
| N-desmethylsildenafil (n= 22) | ||||
| Cmax (ng ml−1) | 104 ± 40.8 | 109 ± 53.1 | 100.70 | 82.72, 122.60 |
| AUC∞ (h ng−1 ml−1) | 425 ± 115 | 440 ± 112 | 105.78 | 96.21, 116.30 |
| t1/2 (h) | 5.14 ± 2.13 | 5.13 ± 1.63 | – | – |
| Tmax (h)‡ | 1.00 | 1.00 | – | – |
| AUC0–t (h ng−1 ml−1) | 389 ± 105 | 372 ± 107 | 112.43 | 98.50, 128.32 |
| Sitaxentan (n= 22) | ||||
| Cmax (µg ml−1) | 10.2 ± 4.73 | |||
| AUC0–t (h µg−1 ml−1) | 25.2 ± 10.2 | |||
| t1/2 (h) | 8.42 ± 1.46 | |||
| Tmax (h)‡ | 2.48 | |||
*
Values are expressed as arithmetic mean ± SD.
†
Statistical comparison of pharmacokinetic parameters between sitaxentan and placebo based on analysis of natural log-transformed data.
‡
Median. AUC, area under the plasma concentration–time curve (AUC0–t was calculated using the linear trapezoidal method where t is the time of last measurable concentration. AUC0–∞ was calculated as AUC0–∞= AUC0–t+ Ct/λ); CI, confidence interval; Cmax, maximum plasma concentration; t1/2, elimination half-life; Tmax, time to maximum plasma concentration.