Parameter estimates from the modeling of the drug depletion data
| Parameter | Propranolol | Prednisolone | Phenacetin | Lidocaine | Ibuprofen | Diclofenac |
|---|---|---|---|---|---|---|
| Individual-donor data | ||||||
| CLint(u)a | 3.88 (28.6%) | 0.81 (14.7%) | 8.91 (12.7%) | 4.38 (12.9%) | 5.02 (16.2%) | 17.80 (16.8%) |
| IDVb | 66.8% (40.9%) | 29.3% (58.1%) | 24.1% (80.4%) | 28.5% (38.1%) | 32.6% (44.9%) | 36.2% (71.5%) |
| IWVb | 32.9% (62.7%) | 21.5% (70.0%) | 26.1% (65.2%) | 11.3% (26.5%) | 30.7% (55.8%) | 6.0% (120.9%) |
| RVb | 21.6% (56.6%) | 10.3% (25.8%) | 14.2% (69.8%) | 8.4% (34.0%) | 9.6% (29.3%) | 20.0% (26.2%) |
| Pooled hepatocytes data | ||||||
| CLint(u)a | 6.34 (5.9%) | 0.91 (4.0%) | 9.67 (17.4%) | 4.24 (3.6%) | 3.54 (33.3%) | 18.60 (14.4%) |
| IWVb | 9.6% (50.4%) | –c | 30.7% (41.5%) | 5.9% (43.7%) | 62.5% (40.0%) | 23.6% (54.4%) |
| RVb | 19.7% (41.1%) | 11.4% (32.0%) | 9.5% (40.4%) | 6.9% (14.4%) | 7.5% (15.8%) | 16.3% (28.6%) |
| Individual-donor/pooled hepatocytes | ||||||
| CLint(u) ratiod | 0.61 (0.27, 0.97) | 0.89 (0.63, 1.16) | 0.92 (0.61, 1.47) | 1.03 (0.77, 1.31) | 1.42 (0.75, 4.20) | 0.96 (0.60, 1.48) |
↵a The typical unbound intrinsic clearance [CLint(u)] for each drug is reported in μl/min/106 cells.
↵b Interdonor variability in unbound intrinsic clearance (IDV), interwell variability in unbound intrinsic clearance (IWV), and the residual variability in the observed data (RV) are reported in terms of CV%, which was calculated as
, where “variance” is the estimate of ω2, π2, and σ2 for IDV, IWV, and RV, respectively (see Materials and Methods). Values in parentheses correspond to relative standard errors calculated as .↵c Interwell variability could not be estimated and was fixed to 0.
↵d Ratio of CLint(u) determined in the individual donor data to the CLint(u) determined in the pooled hepatocytes data. Values in parentheses correspond to 95% confidence intervals of this ratio, calculated using Fieller’s theorem and assuming normality of the CLint(u) estimators. The average CLint(u) ratio across all compounds is 0.97.
