Evaluation of EH vs. EG for eight CYP3A substrates with varying hepatic extraction
| Object | Precipitant | Dose (mg)/Duration (Days) | Reported FG | Extraction Ratio/Ranking | Calculated | Induced/Baseline | Interpretation | ||
|---|---|---|---|---|---|---|---|---|---|
| FG | EH | EH | EG | ||||||
| midazolam | rifampicin | 5/5 or 6 | 0.51 | 0.3–0.5 (intermediate to high) | 0.44 | 0.36 | 1.2 | 0.97 | Similar |
| 10/5 or 6 | 1.3 | 0.98 | Similar | ||||||
| 25/5 or 6 | 1.6 | 1.1 | Similar | ||||||
| 75/5 or 6 | 1.7 | 1.3 | Similar | ||||||
| 600/5 | 0.47 | 0.26 | 2.0 | 1.9 | Similar | ||||
| armodafinil | 100–250/28 | 0.46 | 0.39 | 1.2 | 1.1 | Similar | |||
| pleconaril | 400 (tid)/6 | 0.59 | 0.52 | 1.4 | 0.13 | >Hepatic | |||
| cyclosporine | rifampicin | 600/11 | 0.44 | 0.22 (intermediate) | 0.27 | 0.02 | 1.4 | 1.2 | Similar |
| methadone | rifampicin | 600/10 | 0.78 | 0.09 (low) | 0.69 | 0.10 | 2.8 | 1.2 | >Hepatic |
| alfentanil | rifampicin | 600/4 | 0.60 | 0.14 (low) | 0.61 | 0.29 | 2.5 | 2.0 | Similar |
| rifampicin | 600/5 | 0.62 | 0.26 | 2.6 | 2.0 | Similar | |||
| efavirenz | 600/20 | 0.68 | 0.30 | 1.9 | 1.6 | Similar | |||
| nifedipine | rifampicin | 600/7 | 0.40 | 0.64 (high) | 0.75 | 0.52 | 1.7 | 2.8 | Similar |
| quinidine | rifampicin | 600/7 | 0.90 | 0.4 (high) | 1.0 | 0.24 | 3.7 | 59 | >Gut |
| tacrolimus | rifampicin | 600/18 | 0.14 | low to intermediate | 0.11 | NC | 1.5 | 1.1 | Similar |
| verapamil | rifampicin | 600/13 and 15 | 0.65 | high | 1.0 | 0.86 | 1.1 | 0.2 | >Hepatic |
| phenobarbital | 100/21 | 0.77 | 0.50 | 1.9 | 5.1 | >Gut | |||
EG = gastrointestinal extractionFg, fraction escaping gut metabolism.