Comparison of scaled mycophenolic acid CLint,u,UGT,HKM and predicted CLUGT in scenarios that take different assumptions for physiologic parameters (see Table 2)
Mean values from 20 individual human kidney cortex microsomes are shown, with CVs in parentheses. Data for individual donors are listed (Supplemental Table S3).
| Scenario 1 | Scenario 2 | |
|---|---|---|
| CLint,u,UGT,HKM (µl/min/mg protein) | 1061 (43%) | |
| MPPGK (mg/g kidney) | 11.1a | 28.4 (21%)b |
| Scaled CLint,u,UGT,HKM (ml/min/g kidney) | 11.8 (43%) | 30.2 (53%) |
| Kidney:liver ratio for scaled CLint,u,UGTc | 1.26 (43%) | 3.24 (53%) |
| Kidney weight (g/kg body weight) | 4.5 | 3.1 |
| fu,p | 0.01 | 0.01 |
| RB | 0.6 | 0.6 |
| QR (ml/min/kg) | 16.4 | 13.2 |
| Predicted CLR,met,UGT (ml/min/kg) | 0.83 (41%) | 1.35 (47%) |
| Kidney: liver ratio for predicted CLmet,UGT | 0.29 (41%) | 0.47 (47%) |
| Predicted CLUGT (mL/min/kg)d | 3.70 (9%) | 4.21 (15%) |
| Mean predicted/observed CLUGTe | 0.93 (9%) | 1.06 (15%) |
↵a 11.1 mg/g kidney used for all donors, calculated as weighted (by donor number) mean of values recently reported for mixed kidney and unspecified kidney region (Al-Jahdari et al., 2006; Knights et al., 2016).
↵b Donor-specific MPPGK values measured in the current study used.
↵c CLint,u,UGT,HLM was 9.32 ml/min/g liver, which is based on in vitro measurements in the presence of BSA (Gill et al., 2012).
↵d CLh,met,UGT (2.86 ml/min/kg) calculated per Gill et al. (2012).
↵e Observed CLUGT was 3.97 ml/min/kg (Gill et al., 2012).