Effects of concomitant administration of inhibitors on hepatic intrinsic clearance of midazolam in humans
| Cimetidine | Erythromycin | Itraconazole | ||||
|---|---|---|---|---|---|---|
| − | + | − | + | − | + | |
| fB · CLint(ml/min/kg) | 10.45-a | 7.595-a | 11.35-b | 4.25-b | 13.35-c | 3.05-c |
| 1.37 | 2.7 | 4.4 | |||
| Rpred | ||||||
| Prediction 15-d | 1.030 | 1.025 | 1.009 | |||
| Prediction 25-e | 1.058 | 1.38 | 1.10 | |||
| Prediction 35-f | 1.17 | 1.028 | 1.044 | |||
| Prediction 45-g | 1.33 | 1.59 | 1.56 | |||
| Prediction 55-h | —5-i | 3.3 | — | |||
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Robs, observed R value; Rpred, predicted R value.
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↵5-a Klotz et al., 1985.
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↵5-b Olkkola et al., 1993.
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↵5-c Olkkola et al., 1996.
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↵5-d Prediction using unbound plasma concentration of inhibitors calculated from systemic plasma concentration.
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↵5-e Prediction using unbound liver concentration of inhibitors calculated from systemic plasma concentration.
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↵5-f Prediction using unbound plasma concentration of inhibitors calculated from maximal portal plasma concentration.
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↵5-g Prediction using unbound liver concentration of inhibitors calculated from maximal portal plasma concentration.
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↵5-h Prediction by physiological model based on mechanism-based inhibition.
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↵5-i —, not determined.