Immunoquantified CYP concentrations and RAF estimates in human liver microsomes
| CYP | CYP Content | Index Reaction3-a | RAF | RAF:CYP Content Ratio | r1 (RAF:CYP vs. OR:CYP) | r2 (RAF:CYP vs.b5:CYP) |
|---|---|---|---|---|---|---|
| pmol/mg | pmol/mg | |||||
| 1A2 | 19.2 | EROD | 123.7; (57.3–281.5); [101–152] | 6.8 3-a; (4–15.4); [5.2–7.6] | 0.64 | 0.83 |
| (3.7–55.8) | MROD | 102.9; (46.4–222.8); [84–120] | 5.0 3-a; (3.9–12.5); [4.1–6.1] | 0.65 | 0.83 | |
| [16.6–26.3] | POD | 393.6; (215.5–679.5); [342–479] | 20.5 3-a; (11.3–66.9); [17.2–25.8] | 0.71 | 0.7 | |
| 2B6 | 44.6 | BUP | 160.5; (17.7–756.3); [30–555] | 5.6 3-a; (2.3–17.6); [4.3–9.2] | 0.76 | 0.76 |
| (1.5–148.4) | ||||||
| [2.5–100.9] | ||||||
| 2C19 | 20 | SMH | 29; (4.4–45.1); [20.3–39.6] | 1.48 3-a; (0.87–2.49); [1.3–1.9] | −0.05 (P = NS) | −0.41 (P = NS) |
| (3.1–24.9) | ||||||
| [15.3–22.8] | ||||||
| 3A | 262.4 | TZD | 101.8; (59.3–388.7); [71–256] | 0.6; (0.2–16.5); [0.38–0.85] | 0.7 | 0.78 |
| (3.6–732.5) | DZ | 125.3; (45.9–354.2); [70–247] | 0.56; (0.25–12.8); [0.42–0.89] | 0.66 | 0.83 | |
| [130.5–437.6] | TRZ | 254.1; (100.8–1049.5); [165–583] | 1.35; (0.61–28); [0.96–1.83] | 0.52 (P = .08) | 0.71 | |
| 2D6 | 10.4 | BUF | 8.0; (3.2–30.2); [5.5–13.2] | 0.68; (0.34–1.65); [0.58–1.02] | 0.41 (P = NS) | 0.54 (P = .08) |
| (4.6–41.1) | DMI | 8.9; (4.1–26.3); [6.7–14.8] | 0.83; (0.43–2.03); [0.62–1.17] | 0.66 | 0.76 | |
| [7.2–15.5] | NT | 11.6; (4.1–21.5); [4.8–15] | 0.88; (0.35–2.12); [0.52–1.01] | 0.62 | 0.63 |
n = 12 livers for CYPs 1A2, 2B6, and 3A;n = 10 for CYP2C19, with poor metabolizer livers L11 and L12 excluded; n = 11 livers for CYP2D6, with poor metabolizer liver L8 excluded. Ratios of RAF estimates to immunochemically determined CYP contents are also provided. Boldface entries are sample medians, with range of values in parentheses and interquartile range in brackets. r1 refers to the nonparametric Spearman correlation coefficient between the ratio of RAF to immunochemically determined content of a CYP isoform, and the molar ratio of OR to the CYP isoform. r2 refers to the nonparametric Spearman correlation coefficient between the ratio of RAF to immunochemically determined content of a CYP isoform, and the molar ratio of cytochrome b5 to the CYP isoform. Unless otherwise indicated, P < .05 for Spearman correlation coefficients. NS, nonsignificant.
BUP, bupropion hydroxylation; SMH, S-mephenytoin 4-hydroxylation; TZD, conversion of trazodone to m-CPP; DZ, diazepam 3-hydroxylation; TRZ, triazolam 1-hydroxylation; BUF, bufuralol 1′-hydroxylation; DMI, desipramine 2-hydroxylation; NT, nortriptyline E-10 hydroxylation.
↵3-a Significantly different from unity by Wilcoxon signed rank sum test (P < .05).