Buy Dormicum 7.5mg Pfizer a sleeping tablets characterized by a rapid onset and short duration of action. It also exerts an anxiolytic, anticonvulsant and muscle-relaxant effect.
Absorption : Midazolam is absorbed rapidly and completely after oral administration. With a dose of 15 mg maximum plasma concentrations of 70-120 ng/ ml are reached within one hour. Food prolongs the time to peak plasma concentration by one hour, indicating a reduced absorption rate of midazolam. The absorption half-life is 5-20 minutes . Due to the substantial first-pass effect, absolute bioavailability is 30-50%. The pharmacokinetics of midazolam is linear in the 7.5-15 mg oral dose range.
Distribution : The tissue distribution of midazolam is very rapid and in most cases a distribution phase is not apparent or is essentially finished within 1-2 hours after oral administration. The volume of distribution at steady state is 0.7-1.2L per kg. 96-98% of midazolam is bound to plasma proteins. The major fraction of plasma protein binding is due to albumin. There is a slow and insignificant passage of midazolam into cerebrospinal fluid. In human midazolam has been shown to cross the placenta slowly and to enter fetal circulation. Small quantities of midazolam are found in human milk.
Metabolism: Midazolam is almost entirely eliminated by biotransformation. Less than 1% of the dose is recovered in urine as unchanged drug. Midazolam is hydroxylated by cytochrome P4503A4 isozyme. Hydroxymidazolam is the major urinary and plasma metabolite. 60-80% of the dose is excreted in the urine as glucuroconjugatedhydroxymidazolam. Plasma concentrations of hydroxymidazolam are 30-50% those of the parent compound. After oral administration, there is a substantial first-pass metabolism of 30-60%. The elimination half-life of the metabolite is shorter than 1 hour. Hydroxymidazolam is pharmacologically active and contributes significantly (about 34%) to the effects of oral midazolam. There is no evidence of a genetic polymorphism in the oxidative metabolism of midazolam. Elimination: In young healthy volunteers, the elimination half-life is between 1.5 to 2.5 hours. Midazolam is a non-accumulating drug when given once nightly. Repeated administrations of midazolam do not induce drug-metabolizing enzymes. Pharmacokinetics in special populations : Elderly: Advanced age (above 60 years) has little or no influence on the pharmacokinetics of oral midazolam. Patients with hepatic impairment: Liver cirrhosis has no effect, or may increase the absolute bioavailability of midazolam because of reduced metabolism.