TABLE 1

Physicochemical properties and in vitro inputs for compounds without the potential for biliary excretion as the major clearance pathway

MWlogD7.4pKaPappECCSRB/Pfu,pfu,buffer,BSACLHHEP,appKpHHEPKpHHEP,BSAfu,HLM
g/mol10−6 cm/sμl/min per 106 cells
Diclofenac296.21.24.4 (A)a231a0.660.00380.002667180.950.85
Ibuprofen206.30.9a4.4 (A)a311a0.550.0120.018248.50.210.95
Meloxicam351.40.54.0 (A)351a0.570.00820.0202.1220.920.92
Nateglinide317.41.13.8 (A)a111a0.6b0.0110.0043118.40.200.89a
Tolbutamide270.40.45.1 (A)a261a0.560.0300.0581.80.690.140.91
Atorvastatin558.61.34.4 (A)a1.91bc0.570.0480.0439.488310.46
Bosentan551.61.14.7 (A)7.51b0.670.0280.0345.6448.20.63
Cerivastatin459.61.84.6 (A)141b0.560.0180.01913121120.47
5.5 (B)
Fluvastatin411.51.44.4 (A)111b0.690.00920.02533326.20.70a
Glipizide445.50.44.9 (A)8.81b0.600.0400.0632.03.20.550.95
Glyburide494.02.15.0 (A)141b0.570.00240.007023451.30.65
GSK269984A406.22.12.3 (A)a141b0.650.00240.00081371502.40.24
5.9 (B)a
Irbesartan428.51.44.3 (A)a9.31b0.600.0160.0461450120.76
7.0 (B)a
Montelukast586.25.14.2 (A)a<0.11bc0.670.0000920.000199.61.90.170.00067
5.3 (B)a
Pitavastatin421.51.24.2 (A)a5.71b0.550.00800.05511223.00.67
5.0 (B)a
Repaglinide452.62.24.3 (A)201b0.860.0120.008633641.50.49
5.9 (B)
Telmisartan514.62.44.1 (A)181b0.610.00600.01413440450.57
6.1 (B)
Theophylline180.20.18.6 (B)27 20.710.700.761.20.130.271.0
Timolol316.40.6a8.6 (B)a20 20.820.730.812.66.17.10.83
  • A and B, acidic and basic pKa values; CLHHEP,app, apparent hepatocyte metabolic clearance; ECCS, extended clearance classification system; fu,HLM, unbound fraction in liver microsomes; fu,p, the unbound fraction in plasma; KpHHEP,BSA, hepatocyte to buffer partitioning ratio with BSA; Papp, permeability; RB/P, the blood-to-plasma ratio.

  • a In silico.

  • b Assumed.

  • c On the basis of in vivo PK properties rather than RRCK Papp.