The prolonged sedation from lorazepam may, however, be an acceptable trade-off for its reliable duration of effects, particularly if the person needs to be transferred to another facility. Although lorazepam is not necessarily better than diazepam at initially terminating seizures, lorazepam is, nevertheless, replacing diazepam as the intravenous agent of choice in status epilepticus.Lorazepam serum levels are proportional to the dose administered. Giving 2 mg oral lorazepam will result in a peak total serum level of around 20 ng/mL around two hours later, half of which is lorazepam, half its inactive metabolite, lorazepam-glucuronide. A similar lorazepam dose given intravenously will result in an earlier and higher peak serum level, with a higher relative proportion of unmetabolised (active) lorazepam. On regular administration, maximum serum levels are attained after three days. Longer-term use, up to six months, does not result in further accumulation. On discontinuation, lorazepam serum levels become negligible after three days and undetectable after about a week. Lorazepam is metabolized in the liver by conjugation into inactive lorazepam-glucuronide. This metabolism does not involve liver oxidation, so is relatively unaffected by reduced liver function. Lorazepam-glucuronide is more water-soluble than its precursor, so gets more widely distributed in the body, leading to a longer half-life than lorazepam. Lorazepam-glucuronide is eventually excreted by the kidneys, and, because of its tissue accumulation, it remains detectable, particularly in the urine, for substantially longer than lorazepam. Pharmacodynamics
Relative to other benzodiazepines, lorazepam is thought to have high affinity for GABA receptors, which may also explain its marked amnesic effects.
In the United Kingdom, it is a Class C, Schedule 4 Controlled Drug under the Misuse of Drugs Regulations 2001. Pricing
In 2000, the U.S. drug company Mylan agreed to pay $147 million to settle accusations by the FTC that they had raised the price of generic lorazepam by 2600% and generic clorazepate by 3200% in 1998 after having obtained exclusive licensing agreements for certain ingredients. References
External links
inchem.org – Lorazepam data sheet
benzo.org.uk – Ashton H. Benzodiazepines: How They Work And How to Withdraw. August 2002 (The "Ashton Manual"). "Lorazepam". Drug Information Portal. U.S. National Library of Medicine.