TABLE 2

Summary of the preclinical (rat) and clinical pharmacokinetic data for the 26 compounds


JNJ No.

Species

Dose

Route

CL or CL/F

CLR

VSS or Vd/F

In Vivo t½

Cmax

AUC

Experimentally Determined In Vivo Rat Ptpa
Lung
Adipose
Muscle
Liver
Spleen
Heart
Brain
Kidney
Skin
Testes
Bone
mg l/h liters h ng/ml ng · h/ml
JNJ1 Human 100 i.v. 71.6 413 5.10 1.40E + 03
Human 100 p.o. 202 1.49E + 03 60.1 494
Rat 2.50 i.v. 1.55 3.92 2.91 1.61E + 03 19.4 5.27 6.50 0.571 10.3 2.91 1.52 5.68
Rat 1.88 p.o. 4.24 442
JNJ2 Human 10.0 i.v. 34.3 157 7.59 292
Human 60.0 p.o. 232 2.54E + 03 102 259
Rat 0.625 i.v. 1.30 1.39 0.871 480 10.9 3.21 3.45 13.8 3.87 22.5 4.35
Rat 0.625 p.o. 6.01 104
JNJ3 Human 0.500 i.v. 80.5 1.14E + 03 10.40 6.20
Human 5.00 p.o. 192 2.87E + 03 2.01 26.1
Rat 0.313 i.v. 0.736 1.55 1.37 425 99.7 2.67 2.95 14.1 15.6 4.71 3.73 10.6 7.65 5.32 7.87;14.1
Rat 0.313 p.o. 0.925 338
JNJ4 Human 8.00 i.v. 17.8 3.93 175 7.40 482
Human 8.00 p.o. 18.7 200 42.6 427
Rat 0.625 i.v. 0.473 0.100 1.30 3.48 1.32E + 03 4.42 0.476 2.14 2.53 2.92 2.28 1.51 14.5 1.14 1.46 4.79;4.81
Rat 0.625 p.o. 0.803 778
JNJ5 Human 8.75 i.v. 21.2 28.8 1.37 510
Human p.o.
Rat 4.00E02 i.v. 0.464 0.110 0.146 86.2 1.11 3.01 0.440 1.43 1.05 0.791 0.181 1.18 0.512 0.481
Rat p.o.
JNJ6 Human 0.350 i.v. 49.6 128 2.47 8.10
Human p.o.
Rat 6.25E04 i.v. 1.04 0.967 1.05 0.604 6.18 7.72 1.71 0.370 2.80 1.80 2.08 1.17 1.97
Rat p.o.
JNJ7 Human 10.0 i.v. 33.9 268 14.3 298
Human 20.0 p.o. 71.7 1.48E + 03 71.4 279
Rat 2.50 i.v. 5.75E-02 0.168 2.00 4.35E + 04 1.49 0.562 0.284 2.60 0.911 0.354 0.194 1.53 0.463 0.495 0.19;0.18
Rat 2.50 p.o. 9.82E02 2.55E + 04
JNJ8 Human 5.00 i.v. 2.14 99.0 40.0 2.51E + 03
Human 10.0 p.o. 2.33 134 164 4.30E + 03
Rat 0.625 i.v. 0.400 2.00 2.52 1.56E + 03 27.8 4.29 3.02 21.8 10.5 14.1
Rat 0.625 p.o. 0.918 681
JNJ9 Human 10.0 i.v. 17.0 385 18.9 594
Human 5.00 p.o. 22.7 621 14.5 220
Rat 0.313 i.v. 0.538 1.46 2.13 581 29.2 8.41 0.831 37.7 5.48 2.45 5.37 10.4 2.95 4.62 1.83;7.76
Rat 0.625 p.o. 1.24 506
JNJ10 Human 1.00 i.v. 149 1.33E + 03 7.09 6.58
Human 8.00 p.o. 950 9.72E + 03 0.590 8.42
Rat 2.50 i.v. 2.02 8.37 2.77 1.24E + 03 400 20.1 150 40.2 80.3 80.1 75.1

Rat
10.0
p.o.
5.26




1.90E + 03











JNJ12 Human 30.0 i.v. 16.6 9.24 122 8.20 196
Human 30.0 p.o. 184 2.18E + 03 15.6 163
Rat 1.25 i.v. 0.550 0.300 1.77 2.90 2.27E + 03 7.17 1.01 45.9 2.81 1.02 10.7 1.03
Rat 0.625 p.o. 78.1 8.00
JNJ13 Human 100 i.v. 4.41 30.3 7.54 2.29E + 03
Human 400 p.o. 4.61 50.2 1.71E + 04 8.67E + 04
Rat 2.50 i.v. 3.00E-02 0.194 5.10 8.33E + 04 0.371 0.111 1.39 0.389 0.178 0.251
Rat 2.50 p.o. 4.07E-02 6.15E + 04
JNJ14 Human 50.0 i.v. 59.4 422 10.6 882
Human 200 p.o. 568 8.69E + 03 187 352
JNJ15 Human 2.80 i.v. 25.9 108 4.60
Human 40.0 p.o. 56.4 374 0.650
Rat 1.25 i.v. 0.588 0.433 1.94 2.13E + 03 2.31 8.01 1.49 20.5 1.55 1.52 0.620 7.36 1.12 0.762
Rat 7.50 p.o. 2.96 2.54E + 03
JNJ16 Human 50.0 i.v. 36.0 717 18.9 1.37E + 03
Human 200 p.o. 68.1 1.86E + 03 220 2.94E + 03
Rat 0.500 i.v. 0.370 1.46 2.92 1.35E + 03 46.7 3.24 35.5 20.9 7.73 0.661 14.1 2.35
JNJ17 Human 75.0 i.v. 31.2 172 5.14 2.45E + 03
Human p.o.
Rat 0.500 i.v. 1.40 15.4 6.67 357 56.1 15.3 20.5 48.2 50.4 40.1 1.12 92.3 10.1 2.11
Rat 2.50 p.o.
JNJ18 Human 1.00 i.v. 23.6 0.780 81.0 2.80 45.3
Human 1.00 p.o. 31.3 126 7.90 32.0
Rat 0.313 i.v. 0.962 0.443 0.600 325 3.42 0.581 12.3 0.822 0.233 6.43
Rat 0.313 p.o. 3.52 88.8
JNJ19 Human 0.200 i.v. 1.82 1.26 82.2 33.0 115
Human 2.00 p.o. 1.75 83.4 23.0 1.14E + 03
Rat 2.50E02 i.v. 4.05E02 0.013 0.340 6.00 617 1.49 0.840 0.883 14.0 1.32 1.19 0.589 8.52 0.978 0.982 0.52;1.56
Rat 0.625 p.o. 4.87E02 1.28E + 04
JNJ20 Human i.v. 25.2
Human 15.0 p.o. 56.4 646 9.00 36.1 266
Rat 1.25 i.v. 0.605 0.350 1.59 2.30 2.07E + 03

Rat
2.50
p.o.
1.11




2.24E + 03











mg l/h liters h ng/ml ng · h/ml
JNJ21 Human i.v.
Human 150 p.o. 773 3.04E + 03 21.2 39.3 194
Rat 0.250 i.v. 0.410 2.68 5.86 610 7.25 23.3 6.91 4.35
Rat 1.25 p.o. 1.10 1.14E + 03
JNJ22 Human i.v.
Human 300 p.o. 602 687 1.40 301 498
Rat 6.25 i.v. 0.175 5.25E-02 1.20 3.57E + 04
Rat 10.0 p.o. 0.730 1.37E + 04
JNJ23 Human i.v.
Human 16.0 p.o. 17.9 53.4 3.50 314 894
Rat 0.375 i.v. 0.500 0.369 0.545 750 2.48 2.53 0.665 8.64 3.35 1.34 1.39 4.03 0.915 1.72 0.69;3.79
Rat 1.33 p.o. 1.65 803
JNJ24 Human i.v.
Human 80.0 p.o. 26.5 635 26.6 551 3.02E + 03
Rat 0.625 i.v. 0.829 0.947 2.40 754 3.43 3.36 4.36 27.9 2.53 2.65 1.00 4.89 0.936 4.53 0.58;2.54
Rat 1.25 p.o. 9.77 128
JNJ25 Human i.v.
Human 200 p.o. 19.9 413 22.7 701 1.01E + 04
Rat 0.625 i.v. 0.320 1.735 4.33 1.95E + 03 20.6 3.80 2.27 11.7 6.74 4.27 0.663 2.96 1.09 0.666 0.63;2.44
Rat 1.25 p.o. 0.373 3.35E + 03
JNJ26 Human i.v.
Human 20.0 p.o. 38.8 292 9.80 99 516
Rat 0.625 i.v. 0.365 0.609 1.47 1.71E + 03 2.51 20.0 1.20 2.10 1.10 1.70 0.500 2.00 2.51 2.11 2.72;20.0

Rat
2.50
p.o.
11.1




226











  • a Experimental rat Ptp values were determined under in vivo conditions (single oral or intravenous dose) as the ratio of the AUC calculated over a minimum of five time points, assuming pseudoequilibrium. Underlined values refer to in vivo rat Ptp obtained using total radioactivity measurements.