Enzyme kinetics of Abi, D4A, 5α-Abi, and Gal glucuronidation by human liver and the UGT1A4 enzyme
| Apparent Kma (μM) | Ki (μM) | N | Vmax (pmol/min/mg protein) | Clearance (μl/min/mg protein) | |
|---|---|---|---|---|---|
| Abiraterone | |||||
| Abi-G1 | |||||
| HLM | 2.86 ± 0.25 | 446 ± 34 | 40.96 ± 1.12 | 14.38 ± 0.85 | |
| UGT1A4 | 2.80 ± 0.14 | 645 ± 3 | 43.47 ± 6.54 | 15.51 ± 1.55 | |
| Abi-G2 | |||||
| HLM | 1.10 ± 0.12 | 551 ± 24 | 74.17 ± 3.00 | 67.89 ± 10.25 | |
| UGT1A4 | 0.72 ± 0.10 | 730 ± 216 | 66.75 ± 11.84 | 92.96 ± 3.53 | |
| D4A-G | |||||
| HLM | 4.52 ± 0.09 | 0.93 ± 0.10 | 125.02 ± 27.18 | 27.62 ± 5.49 | |
| UGT1A4 | 7.40 ± 1.36 | 0.81 ± 0.01 | 138.65 ± 11.99 | 19.21 ± 5.15 | |
| 5α-Abi-G | |||||
| HLM | 5.07 ± 0.58 | 446 ± 52 | 206.19 ± 7.28 | 40.79 ± 3.24 | |
| UGT1A4 | 3.92 ± 0.02 | 1712 ± 430 | 222.83 ± 5.87 | 56.82 ± 1.84 | |
| Galeterone | |||||
| Gal-G1 | |||||
| HLM | 3.52 ± 0.84 | 1755 ± 850 | 33.59 ± 1.90 | 9.89 ± 2.90 | |
| UGT1A4 | 4.84 ± 1.20 | 1741 ± 398 | 40.08 ± 6.22 | 8.39 ± 0.79 | |
| Gal-G2 | |||||
| HLM | 1.03 ± 0.25 | 538 ± 42 | 34.41 ± 0.80 | 34.50 ± 9.10 | |
| UGT1A4 | 0.61 ± 0.19 | 419 ± 75 | 34.90 ± 5.44 | 58.14 ± 8.80 | |
↵a Results are expressed as mean ± S.D. of triplicate determinations of at least two independent experiments. Kinetic profiles observed were substrate inhibition for Abi-G1, Abi-G2, 5α-Abi-G, Gal-G1 and Gal-G2, and Hill for D4A-G.