TABLE 3

Rat intravenous pharmacokinetic properties of compounds in the THP series

Series
Compound
log D(7.4)
pKa1
pKa2
Cl
Clu
Vd
Vdu
t1/2
ml/min/kg ml/min/kg l/kg l/kg h
Monobasic 1 1.1 9.2 N.A. 240 >511 6.5 14 0.3
2 1.5 10.4 N.A. 117 >418 6.0 21 0.6
3 1.0 8.9 N.A. 92 >144 7.7 12 1.0
Weakly dibasic 4 1.0 10.4 6.5 93 >245 27 71 3.0
5 1.1 10.4 6.6 78 >181 19 44 2.8
6 0.9 9.3 6.7 122 >244 36 72 3.4
7 0.8 10.4 6.7 134 >268 39 78 3.3
8 1.1 10.0 6.9 128 >492 41 157 3.7
9 1.1 10.4 6.9 41 171 32 97 9.0
10 1.2 10.4 7.6 40 121 62 258 18
11 0.1 10.4 6.6 30 150 12 60 4.6
Strongly dibasic 12 0.1 10.4 9.0 18 86 94 455 60
13 0.2 10.0 10.0 5 15 30 37 31
14 0.2 10.0 9.6 32 178 60 339 22
15 0.3 10.4 9.3 24 186 99 788 48
16
0.4
9.3
9.0
10
59
33
197
39

  • N.A., not applicable.