• M Bolon, R Boulieu, C Flamens, S Paulus, and O Bastien.
• Université Claude Bernard Lyon 1, institut des sciences pharmaceutiques et biologiques, département de pharmacie clinique, de pharmacocinétique et d'évaluation du médicament, 8, avenue Rockefeller, 69373 Lyon, France.
• Ann Fr Anesth Reanim. 2002 Jun 1; 21 (6): 478-92.

ObjectiveReview on midazolam in order to optimize drug utilisation and therapeutic monitoring.Data SourcesResearch of English or French articles published until August 2001, using Medline database. The key words were: midazolam, pharmacokinetics, pharmacodynamic, sedation, drug interaction.Study SelectionOriginal articles, clinical cases and letters to the Editor were selected. Animal studies were excluded.Data ExtractionThe articles were analysed according to their interest in midazolam clinical practice.Data SynthesisMidazolam is a benzodiazepine widely used in intensive care unit, as a sedative, anxiety-relieving, and amnesic drug. Midazolam could be used in patients with cardiac, or respiratory failure, and in neurosurgery. A great interindividual variability on pharmacokinetic and pharmacodynamic response was observed. In intensive care patients, elimination half-life is known to be widely increased. Midazolam is metabolised by hepatic microsomes. The major metabolite is the 1-hydroxymidazolam, which is pharmacologically active. A prolonged sedation due to an accumulation of conjugated metabolite was observed in renal failure patients. Enzymatic inductors or inhibitors could influence pharmacokinetics and pharmacodynamic effects of midazolam.ConclusionAccording to midazolam pharmacokinetic and pharmacodynamic variability, an individual dosage adjustment is essential for long-term sedation. Target controlled sedation could be a mean to limit the variability and to reach quickly the pharmacodynamic effect.

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