Effects of concomitant administration of inhibitors on hepatic metabolic clearance of midazolam in humans
| Cimetidine | Erythromycin | Itraconazole | ||||
|---|---|---|---|---|---|---|
| − | + | − | + | − | + | |
| CLH(ml/min/kg) | 7.354-a | 5.844-a | 7.84-b | 3.64-b | 8.74-c | 2.74-c |
| 1.26 | 2.2 | 3.2 | |||
| Fpred | ||||||
| Prediction 14-d | 1.021 | 1.017 | 1.006 | |||
| Prediction 24-e | 1.043 | 1.26 | 1.066 | |||
| Prediction 34-f | 1.12 | 1.019 | 1.029 | |||
| Prediction 44-g | 1.23 | 1.41 | 1.37 | |||
| Prediction 54-h | —4-i | 2.6 | — | |||
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Fobs, observed F value;Fpred, predicted F value.
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↵4-a Klotz et al., 1985.
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↵4-b Olkkola et al., 1993.
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↵4-c Olkkola et al., 1996.
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↵4-d Prediction using unbound plasma concentration of inhibitors calculated from systemic plasma concentration.
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↵4-e Prediction using unbound liver concentration of inhibitors calculated from systemic plasma concentration.
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↵4-f Prediction using unbound plasma concentration of inhibitors calculated from maximal portal plasma concentration.
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↵4-g Prediction using unbound liver concentration of inhibitors calculated from maximal portal plasma concentration.
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↵4-h Prediction by physiological model based on mechanism-based inhibition.
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↵4-i —, not determined.