Pharmacokinetics dose of R115777 (mg bid)
| . | 100 mg Mean ± SD . | 300 mg Mean ± SD . | 600 mg Mean ± SD . | 900 mg Mean ± SD . | 1 200 mg Mean ± SD . |
|---|---|---|---|---|---|
| Day 1 | |||||
| Tmax, h | 3.2 ± 1.5 | 2.5 ± 1.0 | 2.9 ± 1.1 | 3.9 ± 2.0 | 3.3 ± 1.5 |
| Cmax, ng/mL | 282 ± 221 | 882 ± 224 | 1 728 ± 938 | 1 893 ± 1 549 | 2 615 ± 508 |
| AUC12h, ng · h/mL | 1 573 ± 1 489† | 3 763 ± 810 | 8 898 ± 4 493 | 9 080 ± 9 934 | 14 587 ± 603 |
| T1/2dom, h | 2.4 ± 0.7 | 2.4 ± 0.5 | 3.3 ± 0.7 | 2.9 ± 0.8 | 2.9 |
| No. patients tested | 6 | 5 | 8 | 8 | 3 |
| Day 8 | |||||
| C0h, ng/mL | 46.0 ± 35.6 | 88.8 ± 45.8 | 573 ± 488 | 430 ± 578 | ND |
| Tmax, h | 2.0 ± 0.9 | 1.7 ± 0.6 | 2.6 ± 1.2 | 2.7 ± 1.3 | ND |
| Cmax, ng/mL | 271 ± 165 | 811 ± 305 | 1 840 ± 875 | 1 680 ± 885 | ND |
| AUC12h, ng · h/mL | 1 459 ± 932 | 3 525 ± 1 306 | 10 274 ± 6 440 | 9 056 ± 6 490 | ND |
| Ratio AUC12h | 1.23 ± 0.66 | 0.96 ± 0.19 | 1.4 ± 0.79 | 1.26 ± 0.87 | ND |
| No. patients tested | 6 | 3 | 8 | 8 | 1 |
| Day 15 | |||||
| C0h, ng/mL | 60.7 ± 53.8 | 123 ± 103 | 245 ± 116 | 257 ± 443 | ND |
| Tmax, h | 1.6 ± 1.3 | 2.0 ± 0.0 | 2.3 ± 1.0 | 2.3 ± 1.0 | ND |
| Cmax, ng/mL | 266 ± 208 | 1 048 ± 708 | 1 192 ± 522 | 2 004 ± 1 151 | ND |
| AUC12h, ng · h/mL | 1 235 ± 466 | 4 330 ± 2 792 | 8 079 ± 3 419 | 7 154 ± 3 659 | ND |
| Ratio AUC12h | 1.00 ± 0.61 | 0.87 ± 0.41 | 0.85 ± 0.26 | 1.6 ± 1.46 | ND |
| No. patients tested | 5 | 4 | 5 | 6 | 0 |
| Day 22 | |||||
| T1/2term, h | 35.2 ± 23.0 | 16.4 | 20.3 ± 2.5 | 19.0 ± 5.4 | ND |
| No. patients tested | 3 | 2 | 4 | 3 | 0 |
| . | 100 mg Mean ± SD . | 300 mg Mean ± SD . | 600 mg Mean ± SD . | 900 mg Mean ± SD . | 1 200 mg Mean ± SD . |
|---|---|---|---|---|---|
| Day 1 | |||||
| Tmax, h | 3.2 ± 1.5 | 2.5 ± 1.0 | 2.9 ± 1.1 | 3.9 ± 2.0 | 3.3 ± 1.5 |
| Cmax, ng/mL | 282 ± 221 | 882 ± 224 | 1 728 ± 938 | 1 893 ± 1 549 | 2 615 ± 508 |
| AUC12h, ng · h/mL | 1 573 ± 1 489† | 3 763 ± 810 | 8 898 ± 4 493 | 9 080 ± 9 934 | 14 587 ± 603 |
| T1/2dom, h | 2.4 ± 0.7 | 2.4 ± 0.5 | 3.3 ± 0.7 | 2.9 ± 0.8 | 2.9 |
| No. patients tested | 6 | 5 | 8 | 8 | 3 |
| Day 8 | |||||
| C0h, ng/mL | 46.0 ± 35.6 | 88.8 ± 45.8 | 573 ± 488 | 430 ± 578 | ND |
| Tmax, h | 2.0 ± 0.9 | 1.7 ± 0.6 | 2.6 ± 1.2 | 2.7 ± 1.3 | ND |
| Cmax, ng/mL | 271 ± 165 | 811 ± 305 | 1 840 ± 875 | 1 680 ± 885 | ND |
| AUC12h, ng · h/mL | 1 459 ± 932 | 3 525 ± 1 306 | 10 274 ± 6 440 | 9 056 ± 6 490 | ND |
| Ratio AUC12h | 1.23 ± 0.66 | 0.96 ± 0.19 | 1.4 ± 0.79 | 1.26 ± 0.87 | ND |
| No. patients tested | 6 | 3 | 8 | 8 | 1 |
| Day 15 | |||||
| C0h, ng/mL | 60.7 ± 53.8 | 123 ± 103 | 245 ± 116 | 257 ± 443 | ND |
| Tmax, h | 1.6 ± 1.3 | 2.0 ± 0.0 | 2.3 ± 1.0 | 2.3 ± 1.0 | ND |
| Cmax, ng/mL | 266 ± 208 | 1 048 ± 708 | 1 192 ± 522 | 2 004 ± 1 151 | ND |
| AUC12h, ng · h/mL | 1 235 ± 466 | 4 330 ± 2 792 | 8 079 ± 3 419 | 7 154 ± 3 659 | ND |
| Ratio AUC12h | 1.00 ± 0.61 | 0.87 ± 0.41 | 0.85 ± 0.26 | 1.6 ± 1.46 | ND |
| No. patients tested | 5 | 4 | 5 | 6 | 0 |
| Day 22 | |||||
| T1/2term, h | 35.2 ± 23.0 | 16.4 | 20.3 ± 2.5 | 19.0 ± 5.4 | ND |
| No. patients tested | 3 | 2 | 4 | 3 | 0 |
tmax indicates time to maximum plasma concentration; Cmax, maximum plasma concentration; AUC12h, area under the concentration curve at over 12 hours; T1/2dom, T1/2 dominant; C0h, trough plasma concentration; ND not done; T1/2term, T1/2 terminal.