. 2021 Aug 15;7:16. doi: 10.1186/s40842-021-00130-x

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)

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 [%]

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)

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)

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)

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)

– no descriptive statistics calculated (> 60% of subjects had concentrations below lower limit of quantification), gMean Geometric mean, AT Adipose tissue, C₁₀ Drug concentration 10 h after single dose treatment, C₂₄ Drug concentration 24 h after single dose treatment

* 11beta-HSD1 inhibition in AT defined as % decrease from baseline in d2 cortisol levels