TABLE 3 

Rslope, unbound fraction from flux dialysis, and unbound fraction reference values

CompoundRslope (%CV) s−1 × 10−6Flux Dialysis fuaReported fu (Reference)
Imipramine0.13 (Berry et al., 2011)
38.9 (23%)0.14
Quinidine31.1 (8%)b0.110.22 (Fremstad et al., 1979)
Sertraline9.72 (8%)b0.0350.016 (Ronfeld et al., 1997)
Glecaprevir6.67 (21%)0.0240.025 (AbbVie data on file)
Indomethacin2.61 (13%)0.00940.010 (Indomethacin, 2016)
Nelfinavir0.778 (7%)b0.00280.0042 (Motoya et al., 2006)
Itraconazole0.583 (5%)0.00210.0021 (Riccardi et al., 2015)
Glyburide0.317 (6%)0.00110.0010 (Wan and Rehngren, 2006)
Lapatinib0.211 (10%)0.00076<0.011 (U.S. FDA, 2007)
UCN-010.0247 (1%)0.0000890.000073c (Fuse et al., 1998)
Pibrentasvir0.0172 (33%)0.000062<0.0001 (AbbVie data on file)
Amiodarone0.0158 (8%)0.0000570.00014 (Riccardi et al., 2015)
Bedaquiline0.00806 (15%)0.000029<0.0001 (U.S. FDA, 2012)
Venetoclax0.00333 (32%)0.0000120.000013 (AbbVie data on file)
  • %CV, interassay %CV calculated from experiments conducted on separated days (n = 2–5 experiments); %CV values for flux dialysis fu are identical to Rslope %CV and therefore are not reported separately.

  • a Calculated as Rslope × 3590 s.

  • b Intra-assay %CV calculated from a single experiment run in triplicate.

  • c fu value calculated from published Bmax and KD values (i.e., fu = KD/(KD + Bmax) = 0.0012/(0.0012 + 16.4) = 0.000073).