In vitro and in vivo parameters used for IVIVE of glucuronidation clearance in human liver and kidney microsomes in the absence and presence of 1 or 2% bovine serum albumin
In vivo parameter data represent weighted mean; details of variability between literature reports are given elsewhere (Supplemental Tables 2–6). Predicted CLUGT data represent the mean (±S.D.) of n = 3 for human kidney and liver microsomes.
| Drug | In Vivo Parametersa | fm, UGTb | Derived Parameters | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CLi.v. | Renal CL | fu, p | RB | − BSA | + BSA | Observed CLUGT | Predicted CLUGT | |||||
| HLM Only | HLM + HKM | |||||||||||
| − BSA | + BSA | − BSA | + BSA | − BSA | + BSA | |||||||
| ml · min−1 · kg−1 | ml · min−1 · kg−1 | ml · min−1 · kg−1 | ||||||||||
| Diclofenac | 4.84 | 0.06 | 0.004 | 0.71c | 0.62 | 0.65 | 4.19 | 4.40 | 3.12 (0.49) | 4.48 (0.90) | 3.18 (0.51) | 4.65 (0.93) |
| Gemfibrozil | 1.70 | 0.02 | 0.005c | 0.75c | 0.79 | 0.86 | 1.78 | 1.93 | 1.38 (0.15) | 6.97 (1.64) | 1.48 (0.16) | 7.67 (1.83) |
| Mycophenolic acid | 2.49 | 0.01 | 0.010 | 0.60 | 0.95d | 0.95d | 3.97 | 3.97 | 1.05 (0.06) | 2.84 (0.61) | 1.33 (0.12) | 4.06 (0.78) |
| Naloxone | 21.70 | 0.00 | 0.570 | 1.00e | 0.65 | 0.89 | 14.1 | 19.3 | 3.96 (0.59) | 11.7 (1.83) | 4.31 (0.59) | 13.3 (2.04) |
| Propofol | 27.72f | 0.00 | 0.015 | 0.88 | 0.14 | 0.53 | 3.88 | 14.7 | 0.959 (0.065) | 2.61 (0.17) | 1.05 (0.10) | 3.57 (0.30) |
| Telmisartan | 12.32 | 0.00 | 0.005 | 1.24c | 1.00d | 1.00d | 9.93 | 9.93 | 0.262 (0.014) | 1.28 (0.20) | 0.264 (0.015) | 1.29 (0.20) |
↵a References are listed elsewhere (Supplemental Tables 2–6).
b fm, UGT values taken from in-house data were available.
↵c Measurement made in vitro.
↵d No suitable in vitro data were available so in vivo fm, UGT was used.
↵e No data available; value of 1 assumed for basic drugs.
↵f Blood clearance data.