TABLE 2

Physicochemical properties and in vitro inputs for compounds with 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
Lesinurad404.30.53.1 (A)1.03b0.600.0100.00402.9530.820.68a
Losartan422.91.7a4.5 (A)a1.33b0.620.0290.0179.3567.80.79
PF-05089771500.452.36.0 (A)3.83b0.600.00150.005911342.80.41
PF-05150122541.01.16.5 (A)3.23b0.640.0650.185.8276.30.85
7.4 (B)
PF-05186462531.90.84.1 (A)0.813b0.660.00160.0152.4244.10.67
PF-05241328436.92.03.6 (A)3.93b0.560.00200.0084103002.80.38
Pravastatin424.5−0.44.3 (A)0.313b0.550.630.490.291.79.40.80
Rosuvastatin481.50.14.3 (A)0.753b0.570.160.190.3214240.77
Valsartan435.5−0.83.4 (A)0.323b0.700.00410.00600.58140.880.79
4.7 (A)
Disopyramide339.50.6a9.4 (B)a1.340.700.370.881.23.04.60.94
Maraviroc513.712.09.4 (B)1.840.680.510.331.94.63.30.64
Ranitidine314.4−0.78.5 (B)0.5741.00.841.01.72.11.30.95a
Zolmitriptan287.40.4a8.9 (B)a<0.141b0.750.840.263.04.10.84
  • A and B, acidic and basic pKa values; fu,buffer, unbound fraction in buffer without BSA; fu,buffer,BSA, unbound fraction in buffer with BSA; ECCS, extended clearance classification system; RB/P, the blood-to-plasma ratio.

  • a In silico.

  • b Assumed.