Clonazepam half-life

Ultimately, it is a drug s half-life combined with its potency that dictates its utility as a sedative-hypnotic. Like other benzodiazepines, clonazepam (Klonopin) can be used to treat insomnia, but its long duration of action renders it prone to hangover effects at doses needed to treat insomnia. Nevertheless, low doses of clonazepam (0.25-2 mg) are a treatment for PLMD and are also used to treat RLS. When hangover effects of even low doses of clonazepam are a problem, other benzodiazepines can be used. 

The speciflc clinical use of the numerous available benzodiazepines depends on their individual pharmacokinetic and pharmacodynamic properties. Drugs with a high affinity for the GABAa receptor (alprazolam, clonazepam, lorazepam) have high anxiolytic efficacy drugs with a short duration of action (temazepam) are used as hypnotics to minimise daytime sedative effects. Diazepam has a long half-life and duration of action and may be favoured for long-term use or when there is a history of withdrawal problems oxazepam has a slow onset of action and may be less susceptible to abuse. 

Clonazepam reaches a peak plasma level in 1 to 4 hours. It is metabolized by acetylation, so the half-life ranges from 20 to 80 hours and is dependent on whether a person has a rapid or slow acetylatior phenotype (DeVane et ah, 1991). 

A long half-life is needed for a BZ to be effective as an anticonvulsant to avoid a withdrawal effect. Clonazepam, nitrazepam, and nordazepam are the BZs most often used for their anticonvulsant effects, al-... 

Typical doses of clonazepam have been in the range of 2 to 16 mg/day given on a once or twice per day schedule due to its longer half-life. A major advantage of this anticonvulsant is its relative lack of adverse effects and freedom from laboratory monitoring in comparison with CBZ and VPA. Clonazepam may be more useful when combined with lithium or CBZ rather than as a specific antimanic agent, perhaps supplanting the need for antipsychotics. In this sense, it can be viewed as a behavioral suppressor, rather than a true mood stabilizer (121). 

Alprazolam has been researched more extensively than any other benzodiazepine in panic disorder, and is very effective. Because of its short duration of action, it generally must be administered in three to five daily doses. Clonazepam, which has a longer duration of action than alprazolam, has also been investigated in panic disorder. It can generally be administered twice a day. Clonazepam is reported to have less abuse potential than alprazolam and to be easier to taper during discontinuation owing to its longer half-life. 

Curcumin (1) and its derivatives increased die stability of furosemide, clonazepam, and nifedipin in serum (108), most conspicuously in the case of nifedipin, half-life of which was increased sixfold. This stabilizing effect can be exploited in the formulation of these light sensitive compounds (109). 

Nitrazepam. As indicated previously, nitrazepam (4e), is similar in structure to clonazepam. Absorption after oral administration occurred within 1 h however, in some cases relatively slow absorption (up to 4 h) has been reported (43-48). Rectal administration provided more rapid absorption (median peak time 18 min versus 38 min orally) (48). Although a good correlation was apparent between the volume of distribution and elimination half-life, when comparing the young, elderly, female, and male subjects, the differences observed in volume of distribution related to sex, age, and body weight seem to depend on the relative proportion of body adipose tissue (49). The metabolic pattern of nitrazepam is similar to that of clonazepam, with the principal formation of the inactive 7-amino (41) and 7-acetamido (4m) compounds. 

Clonazepam (8) is almost completely absorbed after oral dosing (96) with an average max of 2-4 h. As with other 7-nitro benzodiazepines, the major metabolic pathway for clonazepam is reduction of the nitro group, acetylation of the resulting amine, and elimination of the acetamide. Hydroxylation of clonazepam or of 7-amino clonazepam to give the 3-hydroxy derivatives represents minor metabolic pathways. The elimination half-life of clonazepam is 20-30 h (97), and no active metabolites are produced. 

Phenobarbital has selective antiseizure activity at low doses and has a long half-life suitable for maintenance treatment in seizure disorders (for characteristics of barbiturates, see sedative-hypnotics). Clonazepam is usually a backup drug in absence and myoclonic seizures it causes marked sedation at anticonvulsant doses. IV lorazepam and diazepam are both used in status epilepticus. 

Clonazepam, in slowly increasing doses up to a maximum of 4 to 6 mg/day given over a 6-week period, had no effect on carbamazepine serum levels. Some patients were also taking phenobarbital. A study in 7 healthy subjects found that carbamazepine 200 mg daily given over a 3-week period reduced the plasma levels of clonazepam 1 mg daily from a range of 4 to 7 nanograms/mL down to 2.5 to 4 nanograms/mL, and reduced the half-life by about one-third. A retrospective analysis of the this interaction in 183 patients found that clonazepam clearance was increased by 22% and carbamazepine clearance was decreased by 20.5% by concurrent use. ... 

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