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Donna Mctavish - One of the best experts on this subject based on the ideXlab platform.

  • Erratum to Zopiclone review
    Drugs & Aging, 2012
    Co-Authors: Alison N. Wadworth, Donna Mctavish
    Abstract:

    Synopsis Zopiclone is a cyclopyrrolone which is chemically unrelated to the benzodiazepines and is thought to act on the GABAA receptor complex at a site distinct from, but closely related to, the benzodiazepine binding site. The hypnotic efficacy of Zopiclone administered as single oral doses has been demonstrated in patients undergoing next-day surgery and in patients with insomnia, and these studies have established an optimal dose of 7.5mg for elderly patients. Using this dose, clinical studies have shown that Zopiclone improved sleep in elderly patients to a similar extent as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg. Studies that also included younger patients have shown that Zopiclone 7.5mg is at least as effective as triazolam 0.25 or 0.5mg, and on most sleep parameters is comparable to temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 20mg. Zopiclone causes minimal impairment to psychomotor performance and mental alertness the morning after night-time administration. The drug is generally well tolerated by patients of all ages; the most frequently reported adverse effects being bitter taste and dry mouth. Treatment withdrawal due to adverse effects is seldom required and reports of rebound insomnia after Zopiclone withdrawal are rare. While symptoms of physical dependence have not been observed in clinical studies, there have been isolated reports of physical dependence in patients with a history of substance abuse. Although the latter finding should be kept in mind, it appears that Zopiclone has a low dependence liability. Thus, with its short duration of action and good tolerability profile, Zopiclone is a well established alternative to the benzodiazepine hypnotics and may be particularly beneficial in those patients unable or unwilling to tolerate the residual effects associated with many other hypnotic agents.

  • Erratum to Zopiclone review
    Drugs & Aging, 1993
    Co-Authors: Alison N. Wadworth, Donna Mctavish
    Abstract:

    Synopsis Zopiclone is a cyclopyrrolone which is chemically unrelated to the benzodiazepines and is thought to act on the GABA_A receptor complex at a site distinct from, but closely related to, the benzodiazepine binding site. The hypnotic efficacy of Zopiclone administered as single oral doses has been demonstrated in patients undergoing next-day surgery and in patients with insomnia, and these studies have established an optimal dose of 7.5mg for elderly patients. Using this dose, clinical studies have shown that Zopiclone improved sleep in elderly patients to a similar extent as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg. Studies that also included younger patients have shown that Zopiclone 7.5mg is at least as effective as triazolam 0.25 or 0.5mg, and on most sleep parameters is comparable to temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 20mg. Zopiclone causes minimal impairment to psychomotor performance and mental alertness the morning after night-time administration. The drug is generally well tolerated by patients of all ages; the most frequently reported adverse effects being bitter taste and dry mouth. Treatment withdrawal due to adverse effects is seldom required and reports of rebound insomnia after Zopiclone withdrawal are rare. While symptoms of physical dependence have not been observed in clinical studies, there have been isolated reports of physical dependence in patients with a history of substance abuse. Although the latter finding should be kept in mind, it appears that Zopiclone has a low dependence liability. Thus, with its short duration of action and good tolerability profile, Zopiclone is a well established alternative to the benzodiazepine hypnotics and may be particularly beneficial in those patients unable or unwilling to tolerate the residual effects associated with many other hypnotic agents. Pharmacological Properties Although structurally unrelated to the benzodiazepines, Zopiclone also binds to regulatory sites on the GABA_A receptor complex in the central nervous system. Zopiclone has marked sedating effects and improves sleep parameters in patients undergoing next-day surgery. Optimum hypnotic activity is achieved with an oral 7.5mg dose. Rebound insomnia after Zopiclone withdrawal is rare and is generally less severe than after withdrawal of flurazepam or temazepam, and less frequent than after flurazepam, nitrazepam or triazolam withdrawal. Zopiclone has limited anxiolytic effects but these have not been evaluated in a clinical setting. Some deterioration of psychomotor function and memory is evident 1 to 2 hours after Zopiclone administration; however, only minimal residual impairment is evident after 8 to 10 hours. Combined administration of alcohol (ethanol) 0.2 to 0.8 g/kg and Zopiclone 7.5mg has an additive effect on impairment of psychomotor function after 1.5 hours which is negligible after 8 hours. Zopiclone does not appear to have any significant effect on respiration. Symptoms of physical dependence have not been observed in studies of psychiatric patients or former alcoholics given Zopiclone in dosages up to 30 mg/day; however, there have been isolated reports of physical dependence in patients with a history of substance abuse. Peak plasma concentrations following a single oral dose of Zopiclone 7. 5mg range from 64 to 86 μg/L and are achieved within 2 hours. Bioavailability is approximately 80% but is increased to 163% in the elderly. Zopiclone undergoes extensive hepatic metabolism; only 4 to 5% is excreted unchanged in the urine and approximately 11% is excreted as a partially active N -oxide metabolite. Plasma Zopiclone clearance is about 14 L/h and is not altered by haemodialysis. In elderly patients (aged >65 years), the elimination half-life of Zopiclone is approximately 8 hours (the elimination half-life of the partially active metabolite is about 6 hours) compared with 3.5 to 6.5 hours in young healthy volunteers. Despite this small increase in half-life, there is no apparent accumulation during repeated administration. Clinical Efficacy The efficacy of Zopiclone in young and elderly patients with insomnia has been well established in noncomparative and placebo-controlled investigations. Results of the largest reported study, a postmarketing surveillance study in 20 513 patients with insomnia (mean age 52.3 years) have shown that oral Zopiclone 3.75 or 7.5 mg/day produced a good to excellent response in about 80% of patients after 21 days. In other studies, Zopiclone produced improvements in sleep parameters in elderly patients with insomnia which were significantly greater than those observed with placebo. Comparative studies have shown that a 7.5mg dose administered on retiring was at least as effective as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg in reducing sleep latency and number of nocturnal awakenings, and in improving sleep duration, sleep quality and morning condition in elderly patients. Other studies, which included younger patients, have reported similar results. Zopiclone 7.5mg was generally at least as effective as triazolam 0.25 or 0.5mg, temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 30mg. Sleep parameters improved in patients with chronic insomnia who were switched from benzodiazepines to Zopiclone. Tolerance to the drug’s hypnotic effects was not observed in the few patients treated with Zopiclone for periods of up to 17 weeks. Tolerability and Overdosage Zopiclone has been generally well tolerated by patients of all ages treated in clinical trials. In the large postmarketing surveillance study described above, adverse events were reported by 9.1% of patients aged 15 to 64 years, 9.5% of patients aged 65 to 79 years and 9.9% of patients aged more than 80 years; 2.8% of all patients withdrew from therapy. The most frequently reported adverse events in this study were bitter taste (3.6%), dry mouth (1.6%) and difficulty arising in the morning (1.3%). Central nervous system depression is the most frequently reported event following voluntary overdosage. Dosage and Administration In elderly patients with chronic insomnia, an initial dosage of 3.75 mg/day is recommended. This can be increased, if necessary, to 7.5 mg/day. This dosage appears to produce optimal hypnotic effects if taken orally 30 to 60 minutes before retiring. A reduced dose (3.75mg) is recommended in patients with hepatic impairment or severe renal insufficiency. Although Zopiclone causes minimal ‘hangover’ effects, patients should be forewarned of the possibility of morning impairment of mental alertness or psychomotor skills following night-time Zopiclone administration.

  • Zopiclone
    Drugs & Aging, 1993
    Co-Authors: Alison N. Wadworth, Donna Mctavish
    Abstract:

    Synopsis Zopiclone is a cyclopyrrolone which is chemically unrelated to the benzodiazepines and is thought to act on the GABA_A receptor complex at a site distinct from, but closely related to, the benzodiazepine binding site. The hypnotic efficacy of Zopiclone administered as single oral doses has been demonstrated in patients undergoing next-day surgery and in patients with insomnia, and these studies have established an optimal dose of 7.5mg for elderly patients. Using this dose, clinical studies have shown that Zopiclone improved sleep in elderly patients to a similar extent as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg. Studies that also included younger patients have shown that Zopiclone 7.5mg is at least as effective as triazolam 0.25 or 0.5mg, and on most sleep parameters is comparable to temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 20mg. Zopiclone causes minimal impairment to psychomotor performance and mental alertness the morning after night-time administration. The drug is generally well tolerated by patients of all ages; the most frequently reported adverse effects being bitter taste and dry mouth. Treatment withdrawal due to adverse effects is seldom required and reports of rebound insomnia after Zopiclone withdrawal are rare. While symptoms of physical dependence have not been observed in clinical studies, there have been isolated reports of physical dependence in patients with a history of substance abuse. Although the latter finding should be kept in mind, it appears that Zopiclone has a low dependence liability. Thus, with its short duration of action and good tolerability profile, Zopiclone is a well established alternative to the benzodiazepine hypnotics and may be particularly beneficial in those patients unable or unwilling to tolerate the residual effects associated with many other hypnotic agents. Pharmacological Properties Although structurally unrelated to the benzodiazepines, Zopiclone also binds to regulatory sites on the GABA_A receptor complex in the central nervous system. Zopiclone has marked sedating effects and improves sleep parameters in patients undergoing next-day surgery. Optimum hypnotic activity is achieved with an oral 7.5mg dose. Rebound insomnia after Zopiclone withdrawal is rare and is generally less severe than after withdrawal of flurazepam or temazepam, and less frequent than after flurazepam, nitrazepam or triazolam withdrawal. Zopiclone has limited anxiolytic effects but these have not been evaluated in a clinical setting. Some deterioration of psychomotor function and memory is evident 1 to 2 hours after Zopiclone administration; however, only minimal residual impairment is evident after 8 to 10 hours. Combined administration of alcohol (ethanol) 0.2 to 0.8 g/kg and Zopiclone 7.5mg has an additive effect on impairment of psychomotor function after 1.5 hours which is negligible after 8 hours. Zopiclone does not appear to have any significant effect on respiration. Symptoms of physical dependence have not been observed in studies of psychiatric patients or former alcoholics given Zopiclone in dosages up to 30 mg/day; however, there have been isolated reports of physical dependence in patients with a history of substance abuse. Peak plasma concentrations following a single oral dose of Zopiclone 7. 5mg range from 64 to 86 μg/L and are achieved within 2 hours. Bioavailability is approximately 80% but is increased to 163% in the elderly. Zopiclone undergoes extensive hepatic metabolism; only 4 to 5% is excreted unchanged in the urine and approximately 11% is excreted as a partially active N -oxide metabolite. Plasma Zopiclone clearance is about 14 L/h and is not altered by haemodialysis. In elderly patients (aged >65 years), the elimination half-life of Zopiclone is approximately 8 hours (the elimination half-life of the partially active metabolite is about 6 hours) compared with 3.5 to 6.5 hours in young healthy volunteers. Despite this small increase in half-life, there is no apparent accumulation during repeated administration. Clinical Efficacy The efficacy of Zopiclone in young and elderly patients with insomnia has been well established in noncomparative and placebo-controlled investigations. Results of the largest reported study, a postmarketing surveillance study in 20 513 patients with insomnia (mean age 52.3 years) have shown that oral Zopiclone 3.75 or 7.5 mg/day produced a good to excellent response in about 80% of patients after 21 days. In other studies, Zopiclone produced improvements in sleep parameters in elderly patients with insomnia which were significantly greater than those observed with placebo. Comparative studies have shown that a 7.5mg dose administered on retiring was at least as effective as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg in reducing sleep latency and number of nocturnal awakenings, and in improving sleep duration, sleep quality and morning condition in elderly patients. Other studies, which included younger patients, have reported similar results. Zopiclone 7.5mg was generally at least as effective as triazolam 0.25 or 0.5mg, temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 30mg. Sleep parameters improved in patients with chronic insomnia who were switched from benzodiazepines to Zopiclone. Tolerance to the drug’s hypnotic effects was not observed in the few patients treated with Zopiclone for periods of up to 17 weeks. Tolerability and Overdosage Zopiclone has been generally well tolerated by patients of all ages treated in clinical trials. In the large postmarketing surveillance study described above, adverse events were reported by 9.1% of patients aged 15 to 64 years, 9.5% of patients aged 65 to 79 years and 9.9% of patients aged more than 80 years; 2.8% of all patients withdrew from therapy. The most frequently reported adverse events in this study were bitter taste (3.6%), dry mouth (1.6%) and difficulty arising in the morning (1.3%). Central nervous system depression is the most frequently reported event following voluntary overdosage. Dosage and Administration In elderly patients with chronic insomnia, an initial dosage of 3.75 mg/day is recommended. This can be increased, if necessary, to 7.5 mg/day. This dosage appears to produce optimal hypnotic effects if taken orally 30 to 60 minutes before retiring. A reduced dose (3.75mg) is recommended in patients with hepatic impairment or severe renal insufficiency. Although Zopiclone causes minimal ‘hangover’ effects, patients should be forewarned of the possibility of morning impairment of mental alertness or psychomotor skills following night-time Zopiclone administration.

  • Zopiclone. A review of its pharmacological properties and therapeutic efficacy as an hypnotic.
    Drugs & aging, 1993
    Co-Authors: Alison N. Wadworth, Donna Mctavish
    Abstract:

    Zopiclone is a cyclopyrrolone which is chemically unrelated to the benzodiazepines and is thought to act on the GABAA receptor complex at a site distinct from, but closely related to, the benzodiazepine binding site. The hypnotic efficacy of Zopiclone administered as single oral doses has been demonstrated in patients undergoing next-day surgery and in patients with insomnia, and these studies have established an optimal dose of 7.5mg for elderly patients. Using this dose, clinical studies have shown that Zopiclone improved sleep in elderly patients to a similar extent as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg. Studies that also included younger patients have shown that Zopiclone 7.5mg is at least as effective as triazolam 0.25 or 0.5mg, and on most sleep parameters is comparable to temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 20mg. Zopiclone causes minimal impairment to psychomotor performance and mental alertness the morning after night-time administration. The drug is generally well tolerated by patients of all ages; the most frequently reported adverse effects being bitter taste and dry mouth. Treatment withdrawal due to adverse effects is seldom required and reports of rebound insomnia after Zopiclone withdrawal are rare. While symptoms of physical dependence have not been observed in clinical studies, there have been isolated reports of physical dependence in patients with a history of substance abuse. Although the latter finding should be kept in mind, it appears that Zopiclone has a low dependence liability. Thus, with its short duration of action and good tolerability profile, Zopiclone is a well established alternative to the benzodiazepine hypnotics and may be particularly beneficial in those patients unable or unwilling to tolerate the residual effects associated with many other hypnotic agents.

Alison N. Wadworth - One of the best experts on this subject based on the ideXlab platform.

  • Erratum to Zopiclone review
    Drugs & Aging, 2012
    Co-Authors: Alison N. Wadworth, Donna Mctavish
    Abstract:

    Synopsis Zopiclone is a cyclopyrrolone which is chemically unrelated to the benzodiazepines and is thought to act on the GABAA receptor complex at a site distinct from, but closely related to, the benzodiazepine binding site. The hypnotic efficacy of Zopiclone administered as single oral doses has been demonstrated in patients undergoing next-day surgery and in patients with insomnia, and these studies have established an optimal dose of 7.5mg for elderly patients. Using this dose, clinical studies have shown that Zopiclone improved sleep in elderly patients to a similar extent as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg. Studies that also included younger patients have shown that Zopiclone 7.5mg is at least as effective as triazolam 0.25 or 0.5mg, and on most sleep parameters is comparable to temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 20mg. Zopiclone causes minimal impairment to psychomotor performance and mental alertness the morning after night-time administration. The drug is generally well tolerated by patients of all ages; the most frequently reported adverse effects being bitter taste and dry mouth. Treatment withdrawal due to adverse effects is seldom required and reports of rebound insomnia after Zopiclone withdrawal are rare. While symptoms of physical dependence have not been observed in clinical studies, there have been isolated reports of physical dependence in patients with a history of substance abuse. Although the latter finding should be kept in mind, it appears that Zopiclone has a low dependence liability. Thus, with its short duration of action and good tolerability profile, Zopiclone is a well established alternative to the benzodiazepine hypnotics and may be particularly beneficial in those patients unable or unwilling to tolerate the residual effects associated with many other hypnotic agents.

  • Erratum to Zopiclone review
    Drugs & Aging, 1993
    Co-Authors: Alison N. Wadworth, Donna Mctavish
    Abstract:

    Synopsis Zopiclone is a cyclopyrrolone which is chemically unrelated to the benzodiazepines and is thought to act on the GABA_A receptor complex at a site distinct from, but closely related to, the benzodiazepine binding site. The hypnotic efficacy of Zopiclone administered as single oral doses has been demonstrated in patients undergoing next-day surgery and in patients with insomnia, and these studies have established an optimal dose of 7.5mg for elderly patients. Using this dose, clinical studies have shown that Zopiclone improved sleep in elderly patients to a similar extent as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg. Studies that also included younger patients have shown that Zopiclone 7.5mg is at least as effective as triazolam 0.25 or 0.5mg, and on most sleep parameters is comparable to temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 20mg. Zopiclone causes minimal impairment to psychomotor performance and mental alertness the morning after night-time administration. The drug is generally well tolerated by patients of all ages; the most frequently reported adverse effects being bitter taste and dry mouth. Treatment withdrawal due to adverse effects is seldom required and reports of rebound insomnia after Zopiclone withdrawal are rare. While symptoms of physical dependence have not been observed in clinical studies, there have been isolated reports of physical dependence in patients with a history of substance abuse. Although the latter finding should be kept in mind, it appears that Zopiclone has a low dependence liability. Thus, with its short duration of action and good tolerability profile, Zopiclone is a well established alternative to the benzodiazepine hypnotics and may be particularly beneficial in those patients unable or unwilling to tolerate the residual effects associated with many other hypnotic agents. Pharmacological Properties Although structurally unrelated to the benzodiazepines, Zopiclone also binds to regulatory sites on the GABA_A receptor complex in the central nervous system. Zopiclone has marked sedating effects and improves sleep parameters in patients undergoing next-day surgery. Optimum hypnotic activity is achieved with an oral 7.5mg dose. Rebound insomnia after Zopiclone withdrawal is rare and is generally less severe than after withdrawal of flurazepam or temazepam, and less frequent than after flurazepam, nitrazepam or triazolam withdrawal. Zopiclone has limited anxiolytic effects but these have not been evaluated in a clinical setting. Some deterioration of psychomotor function and memory is evident 1 to 2 hours after Zopiclone administration; however, only minimal residual impairment is evident after 8 to 10 hours. Combined administration of alcohol (ethanol) 0.2 to 0.8 g/kg and Zopiclone 7.5mg has an additive effect on impairment of psychomotor function after 1.5 hours which is negligible after 8 hours. Zopiclone does not appear to have any significant effect on respiration. Symptoms of physical dependence have not been observed in studies of psychiatric patients or former alcoholics given Zopiclone in dosages up to 30 mg/day; however, there have been isolated reports of physical dependence in patients with a history of substance abuse. Peak plasma concentrations following a single oral dose of Zopiclone 7. 5mg range from 64 to 86 μg/L and are achieved within 2 hours. Bioavailability is approximately 80% but is increased to 163% in the elderly. Zopiclone undergoes extensive hepatic metabolism; only 4 to 5% is excreted unchanged in the urine and approximately 11% is excreted as a partially active N -oxide metabolite. Plasma Zopiclone clearance is about 14 L/h and is not altered by haemodialysis. In elderly patients (aged >65 years), the elimination half-life of Zopiclone is approximately 8 hours (the elimination half-life of the partially active metabolite is about 6 hours) compared with 3.5 to 6.5 hours in young healthy volunteers. Despite this small increase in half-life, there is no apparent accumulation during repeated administration. Clinical Efficacy The efficacy of Zopiclone in young and elderly patients with insomnia has been well established in noncomparative and placebo-controlled investigations. Results of the largest reported study, a postmarketing surveillance study in 20 513 patients with insomnia (mean age 52.3 years) have shown that oral Zopiclone 3.75 or 7.5 mg/day produced a good to excellent response in about 80% of patients after 21 days. In other studies, Zopiclone produced improvements in sleep parameters in elderly patients with insomnia which were significantly greater than those observed with placebo. Comparative studies have shown that a 7.5mg dose administered on retiring was at least as effective as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg in reducing sleep latency and number of nocturnal awakenings, and in improving sleep duration, sleep quality and morning condition in elderly patients. Other studies, which included younger patients, have reported similar results. Zopiclone 7.5mg was generally at least as effective as triazolam 0.25 or 0.5mg, temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 30mg. Sleep parameters improved in patients with chronic insomnia who were switched from benzodiazepines to Zopiclone. Tolerance to the drug’s hypnotic effects was not observed in the few patients treated with Zopiclone for periods of up to 17 weeks. Tolerability and Overdosage Zopiclone has been generally well tolerated by patients of all ages treated in clinical trials. In the large postmarketing surveillance study described above, adverse events were reported by 9.1% of patients aged 15 to 64 years, 9.5% of patients aged 65 to 79 years and 9.9% of patients aged more than 80 years; 2.8% of all patients withdrew from therapy. The most frequently reported adverse events in this study were bitter taste (3.6%), dry mouth (1.6%) and difficulty arising in the morning (1.3%). Central nervous system depression is the most frequently reported event following voluntary overdosage. Dosage and Administration In elderly patients with chronic insomnia, an initial dosage of 3.75 mg/day is recommended. This can be increased, if necessary, to 7.5 mg/day. This dosage appears to produce optimal hypnotic effects if taken orally 30 to 60 minutes before retiring. A reduced dose (3.75mg) is recommended in patients with hepatic impairment or severe renal insufficiency. Although Zopiclone causes minimal ‘hangover’ effects, patients should be forewarned of the possibility of morning impairment of mental alertness or psychomotor skills following night-time Zopiclone administration.

  • Zopiclone
    Drugs & Aging, 1993
    Co-Authors: Alison N. Wadworth, Donna Mctavish
    Abstract:

    Synopsis Zopiclone is a cyclopyrrolone which is chemically unrelated to the benzodiazepines and is thought to act on the GABA_A receptor complex at a site distinct from, but closely related to, the benzodiazepine binding site. The hypnotic efficacy of Zopiclone administered as single oral doses has been demonstrated in patients undergoing next-day surgery and in patients with insomnia, and these studies have established an optimal dose of 7.5mg for elderly patients. Using this dose, clinical studies have shown that Zopiclone improved sleep in elderly patients to a similar extent as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg. Studies that also included younger patients have shown that Zopiclone 7.5mg is at least as effective as triazolam 0.25 or 0.5mg, and on most sleep parameters is comparable to temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 20mg. Zopiclone causes minimal impairment to psychomotor performance and mental alertness the morning after night-time administration. The drug is generally well tolerated by patients of all ages; the most frequently reported adverse effects being bitter taste and dry mouth. Treatment withdrawal due to adverse effects is seldom required and reports of rebound insomnia after Zopiclone withdrawal are rare. While symptoms of physical dependence have not been observed in clinical studies, there have been isolated reports of physical dependence in patients with a history of substance abuse. Although the latter finding should be kept in mind, it appears that Zopiclone has a low dependence liability. Thus, with its short duration of action and good tolerability profile, Zopiclone is a well established alternative to the benzodiazepine hypnotics and may be particularly beneficial in those patients unable or unwilling to tolerate the residual effects associated with many other hypnotic agents. Pharmacological Properties Although structurally unrelated to the benzodiazepines, Zopiclone also binds to regulatory sites on the GABA_A receptor complex in the central nervous system. Zopiclone has marked sedating effects and improves sleep parameters in patients undergoing next-day surgery. Optimum hypnotic activity is achieved with an oral 7.5mg dose. Rebound insomnia after Zopiclone withdrawal is rare and is generally less severe than after withdrawal of flurazepam or temazepam, and less frequent than after flurazepam, nitrazepam or triazolam withdrawal. Zopiclone has limited anxiolytic effects but these have not been evaluated in a clinical setting. Some deterioration of psychomotor function and memory is evident 1 to 2 hours after Zopiclone administration; however, only minimal residual impairment is evident after 8 to 10 hours. Combined administration of alcohol (ethanol) 0.2 to 0.8 g/kg and Zopiclone 7.5mg has an additive effect on impairment of psychomotor function after 1.5 hours which is negligible after 8 hours. Zopiclone does not appear to have any significant effect on respiration. Symptoms of physical dependence have not been observed in studies of psychiatric patients or former alcoholics given Zopiclone in dosages up to 30 mg/day; however, there have been isolated reports of physical dependence in patients with a history of substance abuse. Peak plasma concentrations following a single oral dose of Zopiclone 7. 5mg range from 64 to 86 μg/L and are achieved within 2 hours. Bioavailability is approximately 80% but is increased to 163% in the elderly. Zopiclone undergoes extensive hepatic metabolism; only 4 to 5% is excreted unchanged in the urine and approximately 11% is excreted as a partially active N -oxide metabolite. Plasma Zopiclone clearance is about 14 L/h and is not altered by haemodialysis. In elderly patients (aged >65 years), the elimination half-life of Zopiclone is approximately 8 hours (the elimination half-life of the partially active metabolite is about 6 hours) compared with 3.5 to 6.5 hours in young healthy volunteers. Despite this small increase in half-life, there is no apparent accumulation during repeated administration. Clinical Efficacy The efficacy of Zopiclone in young and elderly patients with insomnia has been well established in noncomparative and placebo-controlled investigations. Results of the largest reported study, a postmarketing surveillance study in 20 513 patients with insomnia (mean age 52.3 years) have shown that oral Zopiclone 3.75 or 7.5 mg/day produced a good to excellent response in about 80% of patients after 21 days. In other studies, Zopiclone produced improvements in sleep parameters in elderly patients with insomnia which were significantly greater than those observed with placebo. Comparative studies have shown that a 7.5mg dose administered on retiring was at least as effective as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg in reducing sleep latency and number of nocturnal awakenings, and in improving sleep duration, sleep quality and morning condition in elderly patients. Other studies, which included younger patients, have reported similar results. Zopiclone 7.5mg was generally at least as effective as triazolam 0.25 or 0.5mg, temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 30mg. Sleep parameters improved in patients with chronic insomnia who were switched from benzodiazepines to Zopiclone. Tolerance to the drug’s hypnotic effects was not observed in the few patients treated with Zopiclone for periods of up to 17 weeks. Tolerability and Overdosage Zopiclone has been generally well tolerated by patients of all ages treated in clinical trials. In the large postmarketing surveillance study described above, adverse events were reported by 9.1% of patients aged 15 to 64 years, 9.5% of patients aged 65 to 79 years and 9.9% of patients aged more than 80 years; 2.8% of all patients withdrew from therapy. The most frequently reported adverse events in this study were bitter taste (3.6%), dry mouth (1.6%) and difficulty arising in the morning (1.3%). Central nervous system depression is the most frequently reported event following voluntary overdosage. Dosage and Administration In elderly patients with chronic insomnia, an initial dosage of 3.75 mg/day is recommended. This can be increased, if necessary, to 7.5 mg/day. This dosage appears to produce optimal hypnotic effects if taken orally 30 to 60 minutes before retiring. A reduced dose (3.75mg) is recommended in patients with hepatic impairment or severe renal insufficiency. Although Zopiclone causes minimal ‘hangover’ effects, patients should be forewarned of the possibility of morning impairment of mental alertness or psychomotor skills following night-time Zopiclone administration.

  • Zopiclone. A review of its pharmacological properties and therapeutic efficacy as an hypnotic.
    Drugs & aging, 1993
    Co-Authors: Alison N. Wadworth, Donna Mctavish
    Abstract:

    Zopiclone is a cyclopyrrolone which is chemically unrelated to the benzodiazepines and is thought to act on the GABAA receptor complex at a site distinct from, but closely related to, the benzodiazepine binding site. The hypnotic efficacy of Zopiclone administered as single oral doses has been demonstrated in patients undergoing next-day surgery and in patients with insomnia, and these studies have established an optimal dose of 7.5mg for elderly patients. Using this dose, clinical studies have shown that Zopiclone improved sleep in elderly patients to a similar extent as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg. Studies that also included younger patients have shown that Zopiclone 7.5mg is at least as effective as triazolam 0.25 or 0.5mg, and on most sleep parameters is comparable to temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 20mg. Zopiclone causes minimal impairment to psychomotor performance and mental alertness the morning after night-time administration. The drug is generally well tolerated by patients of all ages; the most frequently reported adverse effects being bitter taste and dry mouth. Treatment withdrawal due to adverse effects is seldom required and reports of rebound insomnia after Zopiclone withdrawal are rare. While symptoms of physical dependence have not been observed in clinical studies, there have been isolated reports of physical dependence in patients with a history of substance abuse. Although the latter finding should be kept in mind, it appears that Zopiclone has a low dependence liability. Thus, with its short duration of action and good tolerability profile, Zopiclone is a well established alternative to the benzodiazepine hypnotics and may be particularly beneficial in those patients unable or unwilling to tolerate the residual effects associated with many other hypnotic agents.

Jørg Mørland - One of the best experts on this subject based on the ideXlab platform.

  • Zopiclone concentrations in oral fluid and blood after, administration of therapeutic doses of Zopiclone
    Forensic science international, 2017
    Co-Authors: Knut Hjelmeland, Elisabeth Leere Oiestad, Ingebjørg Gustavsen, Åse Marit Leere Øiestad, Gudrun Høiseth, Jørg Mørland
    Abstract:

    Abstract Purpose Little is known about the relationship between concentrations in oral fluid (OF) and blood for the widely prescribed hypnotic drug Zopiclone. The purpose of this study was to investigate the usefulness of OF Zopiclone concentrations to predict blood Zopiclone concentrations in order to introduce OF testing as an alternative to more cumbersome blood testing. Methods 16 healthy young male volunteers received capsules of either 5 or 10 mg Zopiclone on two different study days separated by at least one week. Blood and OF were collected simultaneously at baseline and 9 times after intake of Zopiclone on each study day. In addition an OF sample was collected 24–81 h after intake. Lunch was served between samples taken 2.5 and 3.5 h after intake. All samples were analysed for Zopiclone, and the cut-off was 10 ng/ml in blood and 0.2 ng/ml in OF–buffer mixture. Results Zopiclone was detected in all OF samples during the study day. After 24–81 h, all subjects were also positive for Zopiclone in OF, except from three subjects ingesting the 5 mg dose. In a single case Zopiclone was detected in a baseline OF sample 14 days after intake on an earlier study day. Zopiclone was detected in both OF and blood in 231 OF/blood pairs, and a significant but weak correlation between OF and blood concentration was seen (R 2 of 0.30). The median (range) Zopiclone OF/blood concentration ratio (ZOBCR) for all samples were 3.3 (0.8–18). The ZOBCR decreased when the OF volume increased. After 30 of 31 given doses of Zopiclone, the ZOBCR was higher in samples collected before lunch than samples collected after lunch. Discussion Vast intra- and interindividual differences in ZOBCR were found, and the correlation between OF and blood concentration was less pronounced than reported in former studies. In accordance with earlier studies we found a negative correlation between ZOBCR and OF volume. The ZOBCR decreases in relation to recent intake of a meal, probably because stimulated saliva production causes “dilution” of saliva. OF Zopiclone concentration appeared unsuitable for estimation of blood Zopiclone concentration. Due to long detection time, analysis of Zopiclone in OF might be useful to detect non-recent, previous intake.

  • can a simple clinical test detect impairment of Zopiclone and alcohol a randomized controlled trial
    Forensic Science International, 2015
    Co-Authors: Knut Hjelmeland, Ingebjørg Gustavsen, Jørg Mørland, Jeanpaul Bernard
    Abstract:

    Abstract Purpose The risk of traffic accident involvement is increased among patients prescribed the z-hypnotic drug Zopiclone. Clinical test observations able to indicate drug impairment are therefore essential. This study compared the findings of a simplified clinical test of impairment (SCTI) with those of a battery of computerized psychomotor tests of impairment (CPTI). Methods 16 healthy young male volunteers attended a research unit on four different study days, receiving in randomized order either placebo, Zopiclone 5mg, Zopiclone 10mg, or alcohol 50g. The SCTI was performed twice and the CPTI was performed three times on each study day, with blood samples being collected for drug analysis. Results The SCTI (and the CPTI) was able to demonstrate impairment at 1.5h, but no major impairment was found at 7h with the SCTI, after intake of both Zopiclone and ethanol. The CPTI detected a significantly higher proportion of impaired observations than the SCTI, both for Zopiclone and for ethanol, at all concentration levels. The sensitivity of the clinical tests in detecting blood drug concentrations often associated with impairment, due to Zopiclone (above 23ng/ml) and alcohol (above 0.5g/l), was low, revealing 27 per cent and 18 per cent, respectively. The specificity, however, was higher, both for Zopiclone (88 per cent) and for alcohol (96 per cent). Discussion The SCTI may be a useful tool, especially during roadside investigation, when the police are in doubt as to whether the apprehended driver is impaired or not. A subject, who has consumed Zopiclone or alcohol, tested with the SCTI, with one or more subtests diverging from a habitual result, is likely to have a blood Zopiclone concentration above 23ng/ml or a BAC above 0.5g/l. A negative result, however, is less helpful.

  • Detection of Zopiclone in many drivers--a sign of misuse or abuse
    Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin ny raekke, 1999
    Co-Authors: Jørgen G. Bramness, Svetlana Skurtveit, Jørg Mørland
    Abstract:

    In 1998 Zopiclone had a 42% share of the prescribed hypnotic drug market in Norway. The National Institute of Forensic Toxicology analyses all blood samples from suspected drugged drivers. The rise in Zopiclone prescription was partly reflected in an increase in the number of drivers with Zopiclone detected in the blood. We looked closer at the test results from 101 drivers with Zopiclone detected in their blood in the January 1994 to April 1999 period. 60% had blood concentrations of Zopiclone above the concentration observed after intake of therapeutic doses; 80% had higher blood concentrations than those expected 8 hours after intake of therapeutic doses. The majority of the drivers also tested positive for illegal drugs, prescription drugs with abuse potential, or alcohol. This indicates that Zopiclone is misused or abused. Therefore the same caution should be applied when prescribing Zopiclone as is applied when prescribing e.g. benzodiazepines. Language: no

Knut Hjelmeland - One of the best experts on this subject based on the ideXlab platform.

  • Zopiclone concentrations in oral fluid and blood after, administration of therapeutic doses of Zopiclone
    Forensic science international, 2017
    Co-Authors: Knut Hjelmeland, Elisabeth Leere Oiestad, Ingebjørg Gustavsen, Åse Marit Leere Øiestad, Gudrun Høiseth, Jørg Mørland
    Abstract:

    Abstract Purpose Little is known about the relationship between concentrations in oral fluid (OF) and blood for the widely prescribed hypnotic drug Zopiclone. The purpose of this study was to investigate the usefulness of OF Zopiclone concentrations to predict blood Zopiclone concentrations in order to introduce OF testing as an alternative to more cumbersome blood testing. Methods 16 healthy young male volunteers received capsules of either 5 or 10 mg Zopiclone on two different study days separated by at least one week. Blood and OF were collected simultaneously at baseline and 9 times after intake of Zopiclone on each study day. In addition an OF sample was collected 24–81 h after intake. Lunch was served between samples taken 2.5 and 3.5 h after intake. All samples were analysed for Zopiclone, and the cut-off was 10 ng/ml in blood and 0.2 ng/ml in OF–buffer mixture. Results Zopiclone was detected in all OF samples during the study day. After 24–81 h, all subjects were also positive for Zopiclone in OF, except from three subjects ingesting the 5 mg dose. In a single case Zopiclone was detected in a baseline OF sample 14 days after intake on an earlier study day. Zopiclone was detected in both OF and blood in 231 OF/blood pairs, and a significant but weak correlation between OF and blood concentration was seen (R 2 of 0.30). The median (range) Zopiclone OF/blood concentration ratio (ZOBCR) for all samples were 3.3 (0.8–18). The ZOBCR decreased when the OF volume increased. After 30 of 31 given doses of Zopiclone, the ZOBCR was higher in samples collected before lunch than samples collected after lunch. Discussion Vast intra- and interindividual differences in ZOBCR were found, and the correlation between OF and blood concentration was less pronounced than reported in former studies. In accordance with earlier studies we found a negative correlation between ZOBCR and OF volume. The ZOBCR decreases in relation to recent intake of a meal, probably because stimulated saliva production causes “dilution” of saliva. OF Zopiclone concentration appeared unsuitable for estimation of blood Zopiclone concentration. Due to long detection time, analysis of Zopiclone in OF might be useful to detect non-recent, previous intake.

  • can a simple clinical test detect impairment of Zopiclone and alcohol a randomized controlled trial
    Forensic Science International, 2015
    Co-Authors: Knut Hjelmeland, Ingebjørg Gustavsen, Jørg Mørland, Jeanpaul Bernard
    Abstract:

    Abstract Purpose The risk of traffic accident involvement is increased among patients prescribed the z-hypnotic drug Zopiclone. Clinical test observations able to indicate drug impairment are therefore essential. This study compared the findings of a simplified clinical test of impairment (SCTI) with those of a battery of computerized psychomotor tests of impairment (CPTI). Methods 16 healthy young male volunteers attended a research unit on four different study days, receiving in randomized order either placebo, Zopiclone 5mg, Zopiclone 10mg, or alcohol 50g. The SCTI was performed twice and the CPTI was performed three times on each study day, with blood samples being collected for drug analysis. Results The SCTI (and the CPTI) was able to demonstrate impairment at 1.5h, but no major impairment was found at 7h with the SCTI, after intake of both Zopiclone and ethanol. The CPTI detected a significantly higher proportion of impaired observations than the SCTI, both for Zopiclone and for ethanol, at all concentration levels. The sensitivity of the clinical tests in detecting blood drug concentrations often associated with impairment, due to Zopiclone (above 23ng/ml) and alcohol (above 0.5g/l), was low, revealing 27 per cent and 18 per cent, respectively. The specificity, however, was higher, both for Zopiclone (88 per cent) and for alcohol (96 per cent). Discussion The SCTI may be a useful tool, especially during roadside investigation, when the police are in doubt as to whether the apprehended driver is impaired or not. A subject, who has consumed Zopiclone or alcohol, tested with the SCTI, with one or more subtests diverging from a habitual result, is likely to have a blood Zopiclone concentration above 23ng/ml or a BAC above 0.5g/l. A negative result, however, is less helpful.

  • comparison of Zopiclone concentrations in oral fluid sampled with intercept oral specimen collection device and statsure saliva sampler and concentrations in blood
    Journal of Analytical Toxicology, 2010
    Co-Authors: Hallvard Gjerde, Marit Langodegard, Elisabeth Leere Oiestad, Knut Hjelmeland, Ingebjørg Gustavsen, Åse Marit Leere Øiestad, Jeanpaul Bernard, Asbjorg S Christophersen
    Abstract:

    A clinical study of Zopiclone was performed using doses of 5 and 10 mg. Samples of oral fluid were collected using the Statsure and Intercept devices, and blood samples were collected simultaneously. Concentrations of Zopiclone in samples of oral fluid and blood were determined with liquid chromatography-mass spectrometry, and concentrations in undiluted oral fluid were calculated. The concentrations of Zopiclone in oral fluid were generally higher when using the Intercept compared to the Statsure device; the median oral fluid/whole blood concentration ratios were 3.8 (range 1.5-15.9) and 1.9 (range 1.2-4.6), respectively (n = 21). The correlation between Zopiclone concentrations in oral fluid collected with the two devices was fairly poor, r 2 = 0.35. The results indicate that the type of sampling device may significantly affect the analytical result for Zopiclone in sampled oral fluid.

Pierina Sueli Bonato - One of the best experts on this subject based on the ideXlab platform.

  • enantioselective analysis of Zopiclone in rat brain by liquid chromatography tandem mass spectrometry
    Analytical and Bioanalytical Chemistry, 2013
    Co-Authors: Milena Araujo Tonon, Valquiria Aparecida Polisel Jabor, Pierina Sueli Bonato
    Abstract:

    A new high-performance liquid chromatographic method with triple quadrupole mass spectrometry detection was developed and validated for the quantification of Zopiclone enantiomers in rat brain samples. Zopiclone enantiomers were resolved on a CHIRALPAK AD column with a mobile phase consisting of acetonitrile/ethanol/methanol (60:20:20, v/v/v) at a flow rate of 1.3 mL min-1. Moclobemide was used as internal standard. The sample treatment procedure was carried out employing solid-phase extraction, yielding mean absolute recoveries of 89.6 and 91.7 % for each Zopiclone enantiomer. The validated method showed linearity in the range of 0.29–344.8 ng g−1, with quantification limits of 0.29 ng g−1 for both enantiomers. Precision and accuracy were within acceptable levels of confidence (<15 %). The method was applied in a pilot study of Zopiclone kinetic disposition in rats. It could be observed that the levels of (+)-(S)-Zopiclone were always higher than those of (-)-(R)-Zopiclone, confirming the stereoselective disposition of Zopiclone.

  • enantioselective analysis of Zopiclone and its metabolites in plasma by liquid chromatography tandem mass spectrometry
    Analytical and Bioanalytical Chemistry, 2011
    Co-Authors: Milena Araujo Tonon, Valquiria Aparecida Polisel Jabor, Pierina Sueli Bonato
    Abstract:

    A high-performance liquid chromatographic method with triple-quadrupole mass spectrometry detection (LC-MS-MS) was developed and validated for the first time for the simultaneous quantification of Zopiclone and its metabolites in rat plasma samples. The analytes were isolated from rat plasma by liquid–liquid extraction and separated using a chiral stationary phase based on an amylose derivative, Chiralpak ADR-H column, and ethanol–methanol–acetonitrile (50:45:5, v/v/v) plus 0.025% diethylamine as the mobile phase, at a flow-rate of 1.0 mL min−1. Moclobemide was used as the internal standard. The developed method was linear over the concentration range of 7.5–500 ng mL−1. The mean absolute recoveries were 74.6 and 75.7; 61.6 and 56.9; 72.5, and 70.7 for Zopiclone enantiomers, for N-desmethyl Zopiclone enantiomers and for Zopiclone-N-oxide enantiomers, respectively, and 75.9 for the internal standard. Precision and accuracy were within acceptable levels of confidence (<15%). The method application in a pilot study of Zopiclone kinetic disposition in rats showed that the levels of (+)-(S)-Zopiclone were always higher than those of (−)-R-Zopiclone. Higher concentrations were also observed for (+)-(S)-N-desmethyl Zopiclone and (+)-(S)-N-oxide Zopiclone, confirming the stereoselective disposition of Zopiclone.