Kinetic parameters for formation of α-OHT and N-DMT from TAM, 6β-hydroxytestosterone from testosterone, and 1-hydroxymidazolam from midazolam by CYP3A5-genotyped HLM
| Liver | CYP3A5 Genotype | N-DMT | α-OHT | Midazolam 1-Hydroxylation | Testosterone 6β-Hydroxylation | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Vmax | Km | CLint | Formation CLH | Vmax | Km | CLint | Formation CLH | ||||
| pmol · min−1 · mg protein−1 | μM | μl · min−1 · mg−1 | ml/min | pmol · min−1 · mg protein−1 | μM | μl · min−1 · mg−1 | ml/min | nmol · min−1 · mg−1 | nmol · min−1 · mg−1 | ||
| HH-860 | *1/*1 | 359.11 | 4.32 | 83.15 | 237.24 | 7.31 | 4.55 | 1.65 | 5.55 | 3.25 | 11.5 |
| MCV-36 | *1/*1 | 244.59 | 7.86 | 31.12 | 98.16 | 17.69 | 10.45 | 1.69 | 5.68 | 1.74 | 5.12 |
| CD-8002 | *1/*1 | 236.19 | 10.66 | 22.16 | 71.24 | 1.76 | 12.65 | 0.14 | 0.47 | NA | 1.27 |
| CD-8052 | *1/*1 | 279.36 | 11.08 | 25.21 | 80.52 | 5.44 | 7.65 | 0.71 | 2.39 | NA | 1.6 |
| HH-739 | *1/*1 | 223.41 | 4.15 | 53.83 | 162.05 | 2.71 | 5.97 | 0.45 | 1.52 | 1.2 | 1.6 |
| HH-785 | *1/*1 | 253.76 | 3.32 | 76.43 | 220.10 | 4.2 | 6.0 | 0.7 | 2.36 | 4.1 | 5.8 |
| Mean ± S.D. | 266.07 ± 49.31 | 6.9 ± 3.45 | 48.65 ± 26.64 | 144.88 ± 72.43 | 6.52 ± 5.82 | 7.88 ± 3.09 | 0.89 ± 0.64 | 3.00 ± 2.15 | 2.57 ± 1.34 | 4.48 ± 3.96 | |
| HH-1044 | *1/*3 | 107.41 | 19.42 | 5.53 | 18.43 | 8.49 | 25.82 | 0.33 | 1.11 | 0.841 | 1.22 |
| HH-525 | *1/*3 | 135.96 | 16 | 8.5 | 28.15 | 4.23 | 22.91 | 0.18 | 0.61 | 0.5 | 1.18 |
| HL-G | *1/*3 | 112.92 | 21.52 | 5.25 | 17.51 | 3.2 | 16.52 | 0.19 | 0.64 | 0.8 | ND |
| HL-W | *1/*3 | 92.35 | 7.86 | 11.75 | 38.63 | 3.89 | 16.76 | 0.23 | 0.78 | ND | 1.15 |
| HH-776 | *1/*3 | 69.9 | 17.53 | 3.99 | 13.35 | 5.26 | 29.24 | 0.18 | 0.61 | 0.88 | 1.56 |
| Mean ± S.D. | 103.71 ± 24.55 | 16.47 ± 5.24 | 7 ± 3.12 | 23.22 ± 10.18 | 5.02 ± 2.08 | 22.25 ± 5.59 | 0.22 ± 0.06 | 0.75 ± 0.22 | 0.75 ± 0.17 | 1.28 ± 0.19 | |
| HH-189 | *3/*3 | 112.42 | 3.89 | 28.87 | 91.49 | 2.07 | 0.71 | 2.91 | 9.76 | 2.89 | 13.6 |
| HH-507 | *3/*3 | 89.09 | 5.2 | 17.13 | 55.67 | ND | ND | ND | 0.4 | ||
| XENO | *3/*3 | 52.99 | 4.4 | 12.04 | 39.56 | ND | ND | 0.54 | 0.13 | ||
| HL-D | *3/*3 | 97.32 | 17.44 | 5.58 | 18.60 | 1.8 | 9.62 | 0.19 | 0.64 | 0.25 | 0.59 |
| HL-J | *3/*3 | 122.67 | 9.84 | 12.47 | 40.94 | 5.9 | 8.16 | 0.72 | 2.43 | 0.79 | 2.23 |
| HL-P | *3/*3 | 106.09 | 7.64 | 13.89 | 45.46 | 4.39 | 7.96 | 0.55 | 1.85 | 0.95 | ND |
| HH-689 | *3/*3 | 73.99 | 9.3 | 7.96 | 26.39 | ND | ND | 0.14 | 0.23 | ||
| HL-R | *3/*3 | 153.66 | 13.72 | 11.2 | 36.87 | 7.09 | 12.99 | 0.55 | 1.85 | 0.84 | 2.83 |
| HL-Q | *3/*3 | 64.99 | 7.34 | 8.85 | 29.29 | 3.45 | 6.43 | 0.54 | 1.82 | 0.25 | 0.36 |
| HH-639 | *3/*3 | 76.39 | 5.76 | 13.26 | 43.46 | 2.3 | 6.17 | 0.37 | 1.25 | 0.24 | 0.38 |
| HH-1123 | *3/*3 | 78.11 | 17.63 | 4.43 | 14.80 | 3.65 | 19.77 | 0.18 | 0.61 | 0.67 | 0.52 |
| Mean | 93.43 | 9.29 | 12.33 | 40.23 | 3.83 | 8.98 | 0.75 | 2.53 | 0.75 | 2.13 | |
| S.D. | 28.96 | 4.95 | 6.63 | 20.84 | 1.89 | 5.57 | 0.89 | 2.99 | 0.8 | 4.13 | |
ND, not detected; NA, not available.