In vitro to in vivo scale-up of tacrolimus clearance using liver microsome incubation with both substrate disappearance and metabolite formation approaches
Clearance estimates are reported as the mean (±S.D.) of values from individual livers in each genotype group.
Well Stirred Model | Parallel-Tube Model | |||
|---|---|---|---|---|
| l/h/kg | ||||
| CLDisapp,uHLM→CLHPlasma (Substrate disappearance) | CYP3A5*3/*3 | 0.93 ± 0.11 | 1.16 ± 0.09 | |
| CYP3A5*1/*3 | 1.10 ± 0.06 | 1.24 ± 0.01 | ||
| CLint,uHLM→CLHPlasma (Sum of metabolite formation) | CYP3A5*3/*3 | 0.40 ± 0.14 | 0.48 ± 0.19 | |
|
|
CYP3A5*1/*3
| 0.56 ± 0.08 | 0.70 ± 0.11 | |