Observed and predicted hepatic intrinsic clearance for quercetin, raloxifene, salbutamol, and troglitazone
Predicted clearance was obtained using either individual or combined hepatic sulfation, glucuronidation, and P450 in vitro data.
| Predicted CLint, h | Observed In Vivo CLint, h | |||||
|---|---|---|---|---|---|---|
| Sulfationa | Glucuronidationb | P450 Metabolismb | Combined Approachc | Intravenous | Orald | |
| ml · min−1 · kg−1 | ||||||
| Quercetin | 243 ± 47 | 4289 ± 2528 | N.D. | 4538 ± 2190 | 672 | 633 |
| Raloxifene | 78 ± 45 | 228 ± 176 | 141 ± 28 | 448 ± 153 | 1014 | 1058 |
| Salbutamol | 15.1 ± 7.6 | 8.0 ± 8.0 | 6.6 ± 2.6 | 30 ± 9.5 | 4.7 | 8.1 |
| Troglitazone | 61 ± 24 | 96 ± 68 | 113 ± 96 | 270 ± 100 | 314 | 309 |
N.D., not detected.
↵a SULT predictions were based on mean ± S.D. of three separate experiments using pooled HLC (n = 20).
↵b Based on the mean ± S.D. of in vitro hepatic CLint, UGT and CLint, CYP from three HLM pools (A–C, n = 85). Quercetin and salbutamol values are defined under Materials and Methods. CLint, UGT and CLint, CYP values for raloxifene and troglitazone are from Cubitt et al. (2009).
↵c Sum of CLint, SULT, CLint, UGT, and CLint, CYP values (expressed per gram of liver) was scaled using liver weight of 21.4 g liver/kg.
↵d Calculated from oral clearance data using eq. 6. Fa values for all the drugs are listed under Materials and Methods. FG values estimated from intravenous/oral data are 0.03, 0.12, 0.76, and 0.35 (for quercetin, raloxifene, salbutamol, and troglitazone, respectively).