Parameters (mean ± S.D., n = 3 to 4/group) describing the disposition of 4MU and metabolites 4MUG and 4MUS obtained from compartmental pharmacokinetic analysis of IPL data Nonlinear least-squares regression analysis was performed as described under Materials and Methods based on the model scheme presented in Fig. 1.
Wild-Type Wistar Rat IPLs | Mrp2-Deficient (TR-) Rat IPLs | |||||
|---|---|---|---|---|---|---|
| Control | GF120918 | Control | GF120918 | |||
| ClUP,4MU (ml/min) | 17 ± 2 | 16 ± 1 | 16 ± 1 | 17 ± 1 | ||
| kgluc (min-1) | 2 ± 2 | 3 ± 3 | 3 ± 1 | 2 ± 1 | ||
| ksulf (min-1) | 0.2 ± 0.2 | 0.24 ± 0.06 | 0.4 ± 0.2 | 0.5 ± 0.4 | ||
| kdesulf (min-1) | 0.6 ± 0.3 | 0.6 ± 0.1 | 0.7 ± 0.1 | 0.4 ± 0.4 | ||
| kB/L,4MUG (min-1) | 0.018 ± 0.009 | 0.019 ± 0.007 | 0.08 ± 0.03* | 0.10 ± 0.06* | ||
| kB/L,4MUS (min-1) | 1.5 ± 0.8 | 0.9 ± 0.4 | 2.19 ± 0.04 | 2 ± 1 | ||
| ClUP,4MUG (ml/min) | 0.3 ± 0.4 | 0.4 ± 0.3 | 0.2 ± 0.2 | 0.4 ± 0.2 | ||
| ClUP,4MUS (ml/min) | 3 ± 1 | 1.7 ± 0.7 | 1.4 ± 0.4 | 3 ± 1 | ||
| kbile,4MUG (min-1) | 0.09 ± 0.02 | 0.08 ± 0.03 | 0.0009 ± 0.0004* | 0.0004 ± 0.0002*‡ | ||
| kbile,4MUS (min-1) | 0.10 ± 0.04 | 0.052 ± 0.002 | 0.052 ± 0.004 | 0.001 ± 0.001*‡ | ||