Inter‐ and intraindividual variability in the concentration‐effect (sedation) relationship of flunitrazepam.

Grahnén, A; Wennerlund, P; Dahlström, Bengt; Eckernäs, S.‐Å.

doi:10.1111/j.1365-2125.1991.tb03862.x

Cited by 33 publications

(4 citation statements)

References 10 publications

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“…These results are in agreement with other studies (Grahn6n et al 1991;Ingum et al 1992;Rush et al 1993a, b). Flunitrazepam 2 mg produced the greatest sedation, followed by triazolam 0.50 mg, triazolam 0.25 mg, and flunitrazepam 0.50 mg.…”

Section: Discussionsupporting

confidence: 96%

A comparison of the acute behavioral effects of flunitrazepam and triazolam in healthy volunteers

1996

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Flunitrazepam is an hypnotic benzodiazepine marketed in different European countries. Epidemiological studies have shown that it is frequently abused by opioid addicts. In a survey, "liking" scores for flunitrazepam in methadone maintenance patients were higher than ratings for other benzodiazepines. A double-blind, placebo controlled, crossover clinical trial was conducted to assess the acute behavioral effects of flunitrazepam (0.50 and 2 mg) and triazolam (0.25 and 0.50 mg) in healthy male volunteers. Drug effects on physiological measures, psychomotor performance, and subjective rating scales, including specific questionnaires to evaluate abuse liability (e.g., ARCI or "liking" scores), were assessed before and 6 h after drug administration. Flunitrazepam 2 mg produced the most intense disruptive effects on all the performance tasks, triazolam 0.50 impaired performance except balance. All study drugs at all doses produced sedation symptoms in all or part of the subjective effects questionnaires. Only flunitrazepam 2 mg induced significative increases in some of the scales ("liking", "good effects", "high") that could be related to a possible abuse potential. The results seem to indicate that flunitrazepam, when administered to healthy subjects, produces some pleasurable subjective feelings, that could indicate a higher abuse liability of this drug as compared with other benzodiazepines.

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Section: Discussionsupporting

confidence: 96%

A comparison of the acute behavioral effects of flunitrazepam and triazolam in healthy volunteers

1996

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“…In order of potency, ßunitrazepam 4 mg and triazolam 0.75 mg produced similar impairment, and produced the greatest sedation followed by triazolam 0.50 mg and ßunitrazepam 2 mg. These results are in agreement with other studies in which the e¤ects of these compounds were tested in di¤erent populations (Evans et al 1990;Grahnén et al 1991;Ingum et al 1992Ingum et al , 1994Rush et al 1993a,b;Farré et al 1996).…”

Section: Discussionsupporting

confidence: 94%

Abuse liability of flunitrazepam among methadone-maintained patients

et al. 1998

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Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam 0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales (VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4mg caused euphoria-related effects as measured by increases in ARCI-MBG and "high" scores in the VAS. Our findings of flunitrazepam-induced euphoria in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest that it may be included in the group of benzodiazepines with a relatively high abuse potential.

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“…When compared with the published flunitrazepam pharmacokinetic parameters, the mean half‐life was close to the values reported in adults (20 to 36 hours, 11 25 ± 6 hours, 12 29 ± 11 hours, 3 22.9 ± 6.4 hours, 7 and 25 ± 11 hours 8 ) but longer than the values published in older children (11.8 ± 3.7 hours 4 and 3.98 ± 4.8 hours 9 ). The area under the curve normalized for a same dose was similar to that described in adults by Kanto et al 3 No influence of age on flunitrazepam pharmacokinetics was shown in previous studies that involved elderly poor‐risk patients 7 and healthy adult surgical patients 3 , 8 .…”

Section: Discussionsupporting

confidence: 78%

Pharmacokinetics and tolerance of flunitrazepam in neonates and in infants

Pariente-Khayat

Tréluyer

Rey

et al. 1999

Clinical Pharmacology & Therapeutics

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Inter‐ and intraindividual variability in the concentration‐effect (sedation) relationship of flunitrazepam.

Abstract: 4 The results in young healthy subjects suggest that the present dosage recommendations for temporary insomnia (1-2 mg) may be inappropriate; the dose can probably be reduced to 0.5 mg in some patients to achieve moderate sedation.

Cited by 33 publications

References 10 publications

A comparison of the acute behavioral effects of flunitrazepam and triazolam in healthy volunteers

A comparison of the acute behavioral effects of flunitrazepam and triazolam in healthy volunteers

Abuse liability of flunitrazepam among methadone-maintained patients

Pharmacokinetics and tolerance of flunitrazepam in neonates and in infants

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