Table 3 PK/PD relationship between BI 187004 concentration in adipose tissue and plasma and ex vivo 11beta-HSD1 inhibition in AT after a single dose of BI 187004
Dose (mg) | BI 187004 Plasma C10 gMean (range) [nmol/L] | BI 187004 AT C10 gMean (range) [nmol/L] | BI 187004 AT:plasma ratio (range) 10 h | 11beta-HSD1 inhibition in AT* median (min–max) 10 h [%] | BI 187004 Plasma C24 gMean (range) [nmol/L] | BI 187004 AT C24 gMean (range) [nmol/L] | BI 187004 AT:plasma ratio (range) 24 h | 11beta-HSD1 inhibition in AT* median (min–max) 24 h [%] |
|---|---|---|---|---|---|---|---|---|
10 | 174 (118 – 250) | 17.9 (12.3 – 26.7) | 10.3 (7.78 – 14.8) | 86.8 (81.1 – 91.4) | 71.3 (39.1 – 112) | – (9.91 – 22.6) | – (9.58 – 20.1) | 59.4 (34.0 – 78.6) |
20 | 382 (253 – 529) | 38.1 (26.2 – 49.5) | 9.97 (8.47 – 13.4) | 81.5 (68.5 – 93.6) | 161 (85.8 – 353) | 17.5 (11.1 – 33.3) | 10.8 (5.90 – 16.7) | 82.3 (65.0 – 90.7) |
40 | 796 (467 – 1,140) | 80.3 (67.6 – 122) | 10.1 (7.22 – 14.5) | 95.6 (93.6 – 96.7) | 321 (169 – 625) | 27.5 (18.9 – 42.7) | 8.58 (6.84 – 12.5) | 84.6 (82.9 – 95.0) |
80 | 1,530 (1,040 – 2,570) | 128 (92.3 – 207) | 8.36 (6.71 – 12.2) | 97.5 (95.7 – 98.8) | 878 (605 – 1,560) | 84.5 (63.7 – 128) | 9.62 (8.18 – 12.0) | 93.5 (91.1 – 96.9) |
160 | 3,000 (1,940 – 4,290) | 412 (328 – 58 2) | 13.7 (8.74 – 20.7) | 99.1 (98.8 – 99.4) | 1,630 (1,360 – 2,690) | 168 (105 – 325) | 10.3 (7.73 – 12.4) | 97.9 (94.0 – 98.9) |
240 | 2,600 (313 – 5,800) | 653 (474 – 899) | 25.1 (11.4 – 207) | 99.4 (99.1 – 99.6) | 2,130 (1,530 – 2,630) | 212 (143 – 283) | 9.96 (8.32 – 11.7) | 98.1 (96.8 – 98.8) |
360 | 5,300 (3,360 – 7,680) | 857 (595 – 1,480) | 16.2 (9.31 – 34.4) | 99.5 (99.3 – 99.6) | 2,690 (1,790 – 4,740) | 307 (191 – 404) | 11.4 (8.51 – 15.0) | 98.6 (98.0 – 99.4) |