Table II.
CL Prediction Accuracy
| Authors | Year | Species | Liver model | CLint prediction accuracy | Comments | ||
|---|---|---|---|---|---|---|---|
| Mean fold Error | Percentage within twofold | Predictive tendency | |||||
| Microsomes | |||||||
| Houston and Carlile (37) | 1997 | Rat | Well stirred | 40 | Under-prediction | ||
| Obach (10) | 1999 | Human | Well stirred and parallel tube | WS: 2.3 (a), 4.4 (b), 2.3 (c), PT: 2.3 (a), 4.2 (b), 2.1 (c) | WS: 55 (a), 24 (b), 52 (c) PT: 59 (a), 28 (b), 55 (c) | Under-prediction unless all binding terms are omitted. | Comparison of CL, not CLint, presented. (a) no binding (b) incorporating fub only (c) incorporating both fub and fumic. |
| Ito and Houston (38) | 2004 | Rat | Well stirred, parallel tube, and dispersion | 2.1 (WS), 1.3 (PT), 1.4 (D) | 33 (WS), 39 (PT), 35 (D) | Dispersed around unity | |
| Ito and Houston (55) | 2005 | Human | Well Stirred | 6.17 | 15 | Under-prediction unless fup is omitted | |
| De Buck et al. (54) | 2007 | Rat | Well stirred and parallel tube | WS:1.2 (a), 13.5 (b), 2.5 (c) PT: 1.0 (a), 12 (b), 2.2 (c) | WS:86 (a), 17 (b), 61 (c) PT: 92 (a), 22 (b), 64 (c) | Under-prediction unless all binding terms are omitted | Comparison of CL, not CLint presented. (a) no binding (b) incorporating fub only (c) incorporating both fub and fumic. |
| Naritomi et al. (56) | 2001 | Human | Well stirred, parallel tube, and dispersion | 4 (WS), 3 (PT), 3.2 (D) | 25 (WS), 38 (PT), 50 (D) | Under-prediction | Predictions improved in original manuscript by integration of cross species scaling factor |
| Hepatocytes | |||||||
| Houston and Carlile (37) | 1997 | Rat | Well stirred | 70% | Dispersed around unity | ||
| Parrott et al. (20) | 2005 | Rat | Well stirred | 1.8 | 59 | Dispersed around unity assuming fup = fuinc | Assumes fuhep with diluted serum = fup |
| Germani et al. (53) | 2007 | Rat | Well stirred | 2.3 | 58 | Dispersed around unity assuming fup = fuinc | Comparison of CL, not CLint, presented. Assumes fuhep = fup. blood/plasma ratio assumed = 1 |
| Ito and Houston (38) | 2004 | Rat | Well stirred, parallel tube, and dispersion | 1.4 (WS), 1.3 (PT), 1.1 (D) | 63 (WS), 60 (PT), 66 (D) | Dispersed around unity | |
| Brown et al. (57) | 2007 | Human | Well stirred | 30 | Under-prediction | ||
| McGinnity et al. (58) | 2004 | Human | Well Stirred | 55 | Dispersed around unity assuming fup = fuinc | Assumes fup = fuhep blood/plasma ratio = 1. No acidic compounds | |
| Shibata et al. (59) | 2000 | Rat | Dispersion | 67 | Dispersed around unity assuming fup = fu serum inc | Comparison of CL, not CLint presented. Blood/plasma ratio assumed = 1 | |
| Riley et al. (60) | 2005 | Human | Well stirred | +FCS:86 (a), 3.1 (b), 42 (c) -FCS:13 (a),16 (b), 5.2 (c) | UNDER-PREDICTION unless binding terms are omitted. | Combined dataset from Lave et al. (9), Lau et al. (63), Shibata et al. (59), Naritomi et al. (56). (a) incorporating fub only (b) Assumes fub = fuhep (c) incorporating both fu blood and fu mic. ±FCS indicates the presence/absence of fetal serum albumin | |
| De Buck et al. (24) | 2007 | Human | Well stirred | 2.4 (a) 1.1 (b) | 53 (a) 74 (b) | Under-prediction unless all binding terms are omitted. | NB. Mix of microsome and hepatocyte data presented. (a) Incorporating both fub and fuhep. (b) Assumes fub = fuhep |
WS well stirred, PT parallel tube, D dispersion