Source: Υπουργείο Υγείας (CY) Revision Year: 2019 Publisher: Medochemie Iberia, S.A., Rua Jose Maria Nicolau, no 6, 7oB, São Domingos de Benfica, Lisboa 1500 662, Portugal
Pharmacotherapeutic group: benzodiazepine derivatives
ATC code: N05BA06
Lorazepam is a benzodiazepine. It has anxiolytic, sedative, hypnotic, anticonvulsant and muscle relaxant properties. The exact mechanism of action of benzodiazepines has not yet been fully elucidated. They appear to exert their activity through different mechanisms. Benzodiazepines are likely to exert their effects by binding to specific receptors at different central nervous system sites. Acting like this, they enhance synaptic or presynaptic inhibition achieved by gamma aminobutyric acid, or directly influence the mechanisms responsible for triggering action potentials.
Lorazepam is rapidly absorbed after intramuscular administration. Peak plasma concentrations are reached approximately 60 to 90 minutes after intramuscular administration. The mean elimination half-life of unconjugated lorazepam in human plasma is approximately 12 to 16 hours after intramuscular or intravenous administration. Based on elimination half-life, steady-state concentrations are reached within 3 to 5 days.
The volume of distribution volume is 1.11 l/kg. At clinically relevant concentrations, lorazepam is bound to plasma proteins for approximately 90%.
Lorazepam is metabolized mainly by glucuronic acid conjugation, thereby forming the inactive glucuronide. Lorazepam has no active metabolites. Seventy to seventy-five percent of the dose is excreted in the urine as glucuronide. Lorazepam is not significantly hydroxylated and is also no substrate for the N-desalkylating enzymes of the cytochrome P450 system.
Age has no clinically significant effect on lorazepam kinetics. In one study, a statistically significant decrease in overall clearance was reported in elderly patients, but the elimination half-life was not significantly affected.
In patients with mild to moderate hepatic impairment (hepatitis, cirrhosis due to excessive alcohol consumption) no change in lorazepam clearance was observed.
In single dose pharmacokinetic studies in patients with different degrees of renal insufficiency, ranging from mild to full failure, no significant changes in lorazepam absorption, clearance or excretion were observed. The elimination of the inactive glucuronide metabolite was significantly reduced. In a study in which lorazepam was administered sub-chronically to 2 patients with chronic renal insufficiency, a reduction in elimination and a concomitant prolongation of the elimination half-life of lorazepam was reported. Hemodialysis had no significant effect on the pharmacokinetics of unmetabolized lorazepam but did cause substantial clearance of the inactive plasma glucuronide.
Not applicable.
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