TABLE 2

Experimental in vivo pharmacokinetic data for the 50 compounds

Compound No./Generic Name
p.o. Dosea
i.v. Doseb
CLoral
CLhc
Vdss
t1/2 d
F e
Ptp
Brain
Heart
Kidney
Liver
Lung
Muscle
mg/kg ml/min/kg l/kg h %
JNJ1/Domperidone 2.50 2.50 136 39.2 7.40 1.00 50.0 0.121 3.87 22.5 13.8 10.2 3.45
JNJ2/Nebivolol 10.0 1.25 134 39.1 5.20 1.50 29.0 3.73 4.71 10.6 14.1 99.7 2.95
JNJ3/Galantamine 2.50 2.50 30.1 19.5 5.18 1.51 13.9 2.53 2.14
JNJ4/Lorcainide 7.50 10.0 165 41.4 20.0 3.30 14.0 1.52 2.90 5.67 0.570 19.4 2.82
JNJ5/Fentanyl 0.0330 32.8f 3.65 2.42 3.56 4.54 12.2 3.83 13.6 3.12
JNJ6/Loperamide 2.50 0.630 251 45.3 4.42 1.10 33.0 9.30 5 35.9
JNJ7 2.50 1.25 247 45.1 3.28 0.600 28.0 4.44 18.1 31 11.7 4.40
JNJ8 2.50 0.630 2060 53.8 7.08 5.15 29.7 45.9 12.2
JNJ9/Cisapride 10.0 5.00 375 48.1 4.73 1.04 22.7 1.56 1.93 7.32 17.1 10.8
JNJ10/Ketanserin 10.0 10.0 7.33 6.47 0.670
JNJ11/Ritanserin 10.0 2.50 224 44.3 8.00 2.52 31.0 2.20 10.5 18.6 24 3.02
JNJ12/Risperidone 1.25 1.25 254 45.3 1.77 0.600 27.0
JNJ13/Prucalopride 0.630 0.630 1590 53.3 4.90 0.340 4.00 0.430 4.30 17.6 8.77 10.6 4.57
JNJ14/Sabeluzole 2.50 1.25 76.4 32.1 5.85 2.50 44.0 5.37 10.4 37.7 29.2
JNJ15/Lubeluzole 0.630 33.0f 4.24 2.05 4.13 9.90 27.7 18.1 2.04
JNJ16/Draflazine 5.00 32.6f 2.03
JNJ17 5.00 2.50 34.9 21.4 6.94 4.33 87.0 0.793 4.84 11.7 20.6 2.95
JNJ18/Laniquidar 10.0 5.00 212 43.8 8.95 2.92 28.0 2.86 5.82 12.0 16.8 38.7 7.07
JNJ19 10.0 2.50 275 46.0 2.40 1.40 22.0
JNJ20 5.30 1.50 149 40.3 1.58 0.545 26.0 1.34 1.45 4.47 7.44 0.670
JNJ21 5.00 65.16f 7.35 1.15 1.53 2.95 15.9 3.49 0.486
JNJ22/Norcisapride 10.0 5.00 48.1 25.7 6.34
JNJ23/Paliperidone 6.00 2.50 70.6 31.0 2.03 1.00 58.0
JNJ24 5.00 1.00 57.6 28.2 10.7 5.86 31.9 4.55 7.41 20.9 4.50
JNJ25 10.0 2.00 47.1 25.4 6.47 0.634 3.39 8.25 21.4 22.9 1.47
JNJ26 20.0 5.00 15.0 11.8 4.40 5.20 79.0
JNJ27/Alfentanil 0.160 38.9f 0.346
JNJ28/Sufentanil 0.003 92.8f 4.32 1.05 2.08 1.80 1.17 0.465 6.18 1.71
JNJ29 10.0 2.50 9.08 7.79 12.9 11.6 13.7 25.3 63.8 122 8
JNJ30 10.0 5.00 152 40.5 7.11 2.11 34.0 1.26 2.61 18.1 12 47.7 7.73
JNJ31/Mazapertine 30.0 5.00 3010 54.2 3.15 1.74 3.00
JNJ32 2.50 2.50 443 49.1 28.1 2.89 15.0
JNJ33 10.0 2.50 32.3 20.4 3.00 0.240 3 13.8 8.90 7.80 2.60
JNJ34 10.0 2.50 196 43.1 4.24
JNJ35 10.0 2.50 25.1 17.3 2.40
JNJ36 10.0 2.50 131 38.9 5.50 1.90 41.0
JNJ37 10.0 2.50 1830 53.6 32.7 2.50 34 36 44 212 297 14
JNJ38 5.00 2.50 63.6 29.6 21.2 44.0
JNJ39 2.50 0.630 3640 54.4 1.16 2.60
JNJ40 5.00 2.50 7.18 6.36 6.33 86.0
JNJ41/Itraconazole 10.0 5.00 35.4 21.6 6.47 50.0
JNJ42/Mitratapide 5.00 2.50 265 45.7 4.29 26.0
JNJ43/Rilpivirine 40.0 4.00 108 36.5 4.10 32.0
JNJ44 40.0 25 79.9 32.6 0.210
JNJ45 10.0 1.00 36.3 21.9 9.90 73.9
JNJ46/Tipifarnib 5.00 2.50 872 51.9 2.94 10.0
JNJ47 10.0 2.50 6.10 5.50 1.7 100
JNJ48/Astemizole 10.0 3170 54.3
JNJ49/Liarozole 5.00 29.5 19.2
JNJ50/Loviride
20.0
504
49.8

  • ↵ a Oral dose used for determination of CLoral and F.

  • ↵ b The i.v. dose used for determination of Vdss, F, and terminal in vivo t1/2.

  • ↵ c CLh data were calculated from CLoral using eq. 5.

  • ↵ d Terminal in vivo t1/2 determined after i.v. administration. To directly compare methods Vd1 and Vd2 in their accuracy to predict Vdss and in vivo t1/2, only the basic compounds of Table 1 with an in vitro t1/2 < 60 min were considered.

  • ↵ e Only compounds with experimental solubility data (see Table 1) and an in vitro t1/2 < 60 min were considered for bioavailability (F) predictions.

  • ↵ f For compounds JNJ5, JNJ15, JNJ16, JNJ27, and JNJ28, where only CLtot was available, CLh was assumed to equal CLtot.