Pharmacokinetic-pharmacodynamic modeling of midazolam effects on the human central nervous system.

  title={Pharmacokinetic-pharmacodynamic modeling of midazolam effects on the human central nervous system.},
  author={Richard P. Koopmans and Jasper Dingemanse and Meindert Danhof and G. P. M. Horsten and Chris J van Boxtel},
  journal={Clinical pharmacology and therapeutics},
  volume={44 1},
The effect of midazolam on alpha-activity of the EEG and latency of the P-100 of the visual evoked response (VER) was studied in six healthy subjects. Drug concentration was related to effect with the Emax model that was used with either a threshold drug concentration or a sigmoid exponent. An effect compartment was included in the pharmacokinetic-pharmacodynamic model. Four subjects showed hysteresis, and mean values of half-lives-k(eo) ranged from 0.26 to 0.60 hour. Mean values of EC50 ranged… CONTINUE READING
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