Table 5

Effects of concomitant administration of inhibitors on hepatic intrinsic clearance of midazolam in humans

CimetidineErythromycinItraconazole
+++
fB · CLint(ml/min/kg)10.45-a 7.595-a 11.35-b 4.25-b 13.35-c 3.05-c
Embedded Image 1.372.74.4
Rpred
 Prediction 15-d 1.0301.0251.009
 Prediction 25-e 1.0581.381.10
 Prediction 35-f 1.171.0281.044
 Prediction 45-g 1.331.591.56
 Prediction 55-h 5-i 3.3
  • Robs, observed R value; Rpred, predicted R value.

  • 5-a  Klotz et al., 1985.

  • 5-b  Olkkola et al., 1993.

  • 5-c  Olkkola et al., 1996.

  • 5-d  Prediction using unbound plasma concentration of inhibitors calculated from systemic plasma concentration.

  • 5-e  Prediction using unbound liver concentration of inhibitors calculated from systemic plasma concentration.

  • 5-f  Prediction using unbound plasma concentration of inhibitors calculated from maximal portal plasma concentration.

  • 5-g  Prediction using unbound liver concentration of inhibitors calculated from maximal portal plasma concentration.

  • 5-h  Prediction by physiological model based on mechanism-based inhibition.

  • 5-i  —, not determined.