Skip to main content

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

From: Safety, tolerability, pharmacokinetics and pharmacodynamics of single oral doses of BI 187004, an inhibitor of 11beta-hydroxysteroid dehydrogenase-1, in healthy male volunteers with overweight or obesity

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)
  1. – 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
  2. * 11beta-HSD1 inhibition in AT defined as % decrease from baseline in d2 cortisol levels