PMID: 2109472Jan 1, 1990Paper

Pharmacology of Dormicum (midazolam) and Anexate (flumazenil)

Acta Anaesthesiologica Scandinavica. Supplementum
R Amrein, W Hetzel

Abstract

Midazolam and flumazenil have some characteristics in common which make them suitable partners as benzodiazepine (BZD) agonist and antagonist. After intravenous (i.v.) administration, both drugs are rapidly distributed into similar distribution volumes, from which they are cleared with a comparable short elimination half-life (t1/2 beta) in the range of 1 h (flumazenil) to 3 h (midazolam). Both drugs undergo hepatic metabolisation with a relatively high hepatic extraction ratio of around 0.3 for midazolam and 0.6 for flumazenil. The metabolisation of midazolam and flumazenil may equally be affected by considerable loss of active liver cells or by temporarily reduced hepatic blood flow. In such a case, elimination of both drugs may be prolonged in the same way. Flumazenil has only an inactive metabolite. The main active alpha-hydroxy-metabolite of midazolam does not contribute much to the activity of midazolam after parenteral administration. Its potency is lower than that of midazolam and its shorter elimination half-life (0.8 h) does not prolong the activity of the parent drug. As indicated by the therapeutic index, both drugs have a very high safety margin, which is considerably higher than that of thiopentone or propofol. On...Continue Reading

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