The rates of probe substrate metabolism in freshly isolated human lung parenchymal cells
Substrate concentration was 2 μM.
Substrate | Enzyme | In Vitro Clearance | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Donor 1 | Donor 2 | Donor 3 | Donor 4 | Donor 5 | Donor 6 | Donor 7 | Donor 8 | |||||||||
| μl/min/106 cells | ||||||||||||||||
| Probe Substrates | ||||||||||||||||
| 7-EC | CYP1A | 0.70 | N.D. | N.D. | 1.50 | N.D. | N.D. | 1.75 | N.D. | |||||||
| ER | CYP1A | — | 2.48 | 1.34 | 1.10 | — | — | — | 1.38 | |||||||
| Coumarin | CYP2A6 | 1.66 | 2.42 | N.D. | N.D. | N.D. | — | — | N.D. | |||||||
| Bupropion | CYP2B6 | — | — | — | — | 0.46 | 2.79 | 0.67 | N.D. | |||||||
| Diclofenac | CYP2C9 | N.D. | — | — | N.D. | — | — | — | — | |||||||
| S-Mephenytoin | CYP2C19 | N.D. | — | — | N.D. | — | — | — | — | |||||||
| Bufuralol | CYP2D6 | 0.76 | — | — | — | — | 4.01 | 1.38 | — | |||||||
| Astemizole | CYP2F1/2J2 | — | 1.66 | 3.04 | 1.10 | 2.10 | — | — | — | |||||||
| Midazolam | CYP3A4 | N.D. | — | 1.06 | 0.94 | 2.92 | — | — | 1.42 | |||||||
| Testosterone | CYP3A4 | — | — | 1.16 | — | — | 2.76 | 0.20 | — | |||||||
| 7-HC | Phase II | 0.68 | 1.92 | 1.66 | N.D. | 0.36 | — | — | 1.42 | |||||||
| Naphthol | Phase II | — | — | — | — | 0.68 | ∏ | ∏ | 3.54 | |||||||
| 4-MU | Phase II | — | — | — | — | — | 0.44 | 1.08 | N.D. | |||||||
| Acetaminophen | Phase II | — | — | — | — | — | 3.72 | 2.22 | — | |||||||
| BDP | Esterase | 17 | 40 | 84 | 44 | 16 | 22 | 18 | 19 | |||||||
| Inhaled Drugs | ||||||||||||||||
| Salbutamol | Phase II | — | — | — | — | — | 2.12 | N.D. | 0.39 | |||||||
| Budesonide | CYP3A4 | — | — | — | — | — | 0.40 | N.D. | N.D. | |||||||
| Formoterol | Phase II | — | — | — | — | 2.40 | 3.84 | N.D. | N.D. | |||||||
—, experiment not performed; N.D., turnover not detected (assay limit of quantitation 0.5 μl/min/106), ∏, turnover observed but not quantified.