TABLE 1

Predicted clearance rates in MPCCs for 26 drugs

Donor 1 is the RTM lot. Asterisks indicate that Donor 2 was Hu4163, rather than JNB. N/A, not available owing to cell-sourcing limitations. The in vivo pharmacokinetic parameters were compiled from several sources, including: Obach (1999), Lau et al. (2002), McGinnity et al. (2004), Brown et al. (2007), Obach et al. (2008), Brunton et al. (2011), Chan et al. (2013).

In Vivo Observed Pharmacokinetic ParametersPredicted Clearance in MPCCs
fu = Reported Literature Valuesfu = 1
Compound NameKnown Routes of MetabolismIn Vivo ClearancefuDonor 1Donor 2AverageDonor 1Donor 2Average
ml/min per kilogramml/min per kilogram
VerapamilCYP3A4, 2C919.50.106.796.866.8317.3617.4117.39
Sumatriptan190.8312.3613.7413.0513.2914.6013.95
NaloxoneUGT2B7180.5414.4514.5214.4916.8716.9216.90
PropranololCYP2D6, 1A215.70.136.704.955.8316.4414.7715.61
Metoprolol*CYP2D6130.883.805.764.784.295.374.83
Triprolidine*130.503.307.785.545.7011.358.52
Desipramine*CYP2D6, 1A2; UGT10.30.162.252.392.328.999.349.16
TimololCYP2D610.10.905.39N/A5.395.82N/A5.82
DextromethorphanCYP2D6, 3A4, 1A2, 2C198.60.5010.6611.3911.0314.1414.7714.46
OmeprazoleCYP2C19, 3A48.40.052.532.472.5015.3815.2615.32
Imipramine*CYP2D6, 1A2, 2C19, 3A4; UGT1A480.10N/A2.062.06N/A10.9310.93
DiclofenacCYP2C97.60.010.08N/A0.088.90N/A8.90
ZolmitriptanCYP1A26.70.751.943.012.482.513.833.17
MethylprednisoloneCYP3A46.10.234.676.575.6211.6413.9512.80
ErythromycinCYP3A45.60.100.711.060.895.447.306.37
ZiprasidoneCYP3A45.10.000.100.100.1016.6616.6316.65
Betaxolol*4.80.400.830.210.524.203.153.67
Prednisolone*CYP3A42.90.250.680.590.643.363.083.22
Furosemide*1.70.010.030.040.042.512.742.63
TheophyllineCYP1A21.10.410.340.260.300.810.620.72
LorazepamUGT10.090.460.430.454.153.974.06
DiazepamCYP2C19, 1A2, 3A40.530.020.210.220.226.306.696.50
TolbutamideCYP2C9, 2C190.380.050.210.400.313.495.844.67
NaproxenCYP2C9, 1A20.190.010.180.490.349.7514.7812.27
MeloxicamCYP2C9, 3A40.120.010.010.030.021.383.982.68
Warfarin*CYP2C9, 3A40.050.020.040.020.031.851.021.44
Within 2-fold32%25%31%60%63%62%
Within 3-fold48%58%58%68%71%73%
Within 4-fold64%71%69%76%79%77%
  • UGT, uridine 5′-diphospho-glucuronosyltransferase.