Dormicum Mechanism of Action

Short-acting benzodiazepine for premedication, sedation, induction and maintenance of anesthesia.
Tablet: Sleep-inducing agent.
Pharmacology: Midazolam has a very rapid sedative and sleep-inducing action of pronounced intensity. It also exerts an anxiolytic, an anticonvulsant and a muscle-relaxant effect.
Ampoule: Midazolam is a derivative of the imidazobenzodiazepine group. The free base is a lipophilic substance with low solubility in water.
The basic nitrogen in position 2 of the imidazobenzodiazepine ring system enables midazolam to form water-soluble salts with acids. These produce a stable and well-tolerated injection solution.
The pharmacological action of midazolam is characterized by rapid onset, and because of rapid metabolic transformation, short duration. Because of its low toxicity, midazolam has a wide therapeutic range.
After parenteral administration, anterograde amnesia of short duration occurs (the patient does not recall events that occurred during the peak of activity of the compound).
Pharmacokinetics: Tablet: Absorption: Dormicum is absorbed rapidly and completely after oral administration. Due to the first-pass effect, bioavailability is approximately 40%.
With a dose of 15 mg, a C_max of 70-120 ng/mL is reached at T_max 0.5-1.5 hrs.
Distribution: The concentrations in the plasma decrease in 2 phases with half-lives of 0.3-0.5 hrs (distribution phase) and 1.5-3.5 hrs (elimination phase). 96-98% of midazolam becomes bound to plasma proteins. The volume of distribution ranges from 0.7-1.2 L/kg.
Metabolism: Midazolam is rapidly and completely metabolized. 30-50% of the active ingredient is already metabolized in the course of the first passage through the liver.
The main pharmacologically active metabolite is α-hydroxy midazolam, the elimination half-life of which is shorter than that of the parent substance.
There is no accumulation of midazolam or its active metabolites on prolonged once-daily administration.
Elimination: Midazolam is eliminated via metabolism. The metabolites formed undergo conjugation with glucuronic acid and are eliminated as glucuronides via the kidneys.
Ampoule: Absorption After IM Injection: Absorption of midazolam from the muscle tissue is rapid and complete. Maximum plasma concentrations are reached within 30 min. Bioavailability is over 90%.
Distribution: When midazolam is injected IV, the plasma concentration-time curve shows 2 distinct phases of distribution. The volume of distribution calculated under steady-state conditions is 0.7-1.2 L/kg body weight. Studies show a protein-binding of 96-98%.
In animals and humans, midazolam has been shown to cross the placenta and to enter fetal circulation. Small quantities of midazolam are found in human milk.
Metabolism: Midazolam is metabolized rapidly and completely. The primary metabolite is a α-hydroxy-midazolam. The fraction of the dose extracted by liver has been estimated at 40-50%. Many medicaments have been found to inhibit the production of this metabolite in vitro. For some of these drugs, this has been confirmed in vivo (see Interactions).
Elimination: In healthy volunteers, the elimination half-life is between 1.5 and 2.5 hrs. Plasma clearance is in the range of 300-400 mL/min. When midazolam is given by IV infusion, its elimination kinetics do not differ from those following bolus injection. The elimination half-life of the main metabolite, α-hydroxy-midazolam, is shorther than that of the parent substance. It is conjugated with glucuronic acid (inactivation). The metabolites are renally excreted.
Pharmacokinetics in Special Clinical Situations: In adults >60 years, the elimination half-life may be prolonged up to 3 times and in some intensive-care patients requiring midazolam by IV infusion for long-term sedation, up to 6 times. In these patients, infusion at an unchanged rate results in higher plasma levels at steady state.
The elimination half-life may also be prolonged in patients with congestive heart failure and with reduced hepatic function.
In children (3-10 years), the elimination half-life is between 1 and 1.5 hrs.
In neonates, the half-life of elimination is prolonged with a mean of 6 hrs (3-12 hrs) due to liver immaturity.