Dynamics and Kinetics of a Modified‐Release Formulation of Zolpidem: Comparison With Immediate‐Release Standard Zolpidem and Placebo

Greenblatt, David J.; Legangneux, Eric; Harmatz, Jerold S.; Weinling, Estelle; Freeman, Jon; Rice, Kathleen; Zammit, Gary

doi:10.1177/0091270006293303

Cited by 55 publications

(50 citation statements)

References 43 publications

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“…36 We do not believe residual sedation accounts for the reduced SDMC with zolpidem-ER 12.5 mg. since testing was done 9.5 hours post-dose and studies of this drug as a hypnotic indicate no residual sedation 8.5 to 9.5 hours post dosing. 25,26,37 Although DSST scores with zolpidem-ER were slightly lower than those with zaleplon and placebo, follow-up correlational analyses between DSST and WPT/FTT performance showed no significant findings, indicating that any residual sedation present in the zolpidem-ER condition did not predict performance on the memory tests. We also visually examined the data to determine if residual sedation was more likely to occur in females, since the FDA has recently lowered the recommended dosage of zolpidem-ER for women based on reports that some women eliminate zolpidem more slowly than men.…”

Section: Discussionmentioning

confidence: 89%

The Effect of Two Benzodiazepine Receptor Agonist Hypnotics on Sleep-Dependent Memory Consolidation

Hall-Porter

Schweitzer

Eisenstein

et al. 2014

Journal of Clinical Sleep Medicine

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Results: ANOVA revealed a signifi cant condition effect for the WPT (p = 0.025) and a trend for the FTT (p = 0.067), which was signifi cant when sex was added to the model (p = 0.014). Improvement in memory performance following sleep was lower with bedtime dosing of zolpidem-ER compared to placebo and middle-of-the-night dosing of zaleplon. There were no differences between placebo and zaleplon. Conclusions:The results suggest that in some circumstances hypnotics may have the potential to reduce the degree of sleep-dependent memory consolidation and that drug-free sleep early in the night may ameliorate this effect. S C I E N T I F I C I N V E S T I G A T I O N SA growing body of evidence demonstrates that sleep promotes memory consolidation in healthy individuals.1-3 Numerous studies using various designs and memory tasks have consistently found that memory consolidation (i.e., improvement on a given memory task from initial training/test to retest) is significantly greater after a period of sleep than a period of wake. This is commonly referred to as sleep-dependent memory consolidation (SDMC). 4 For example, improvements on a procedural memory fi nger-tapping task were observed after a night of sleep but not after 4-, 8-, or 12-hour daytime periods without sleep. 5,6 Studies examining declarative memory consolidation, such as with a word pair association task, also demonstrate improvements in performance after sleep.7 In addition to improvements in memory following overnight sleep, memory consolidation is also enhanced during naps as short as 45 minutes. Improvements in procedural 8,9 and declarative 10 memory occur with naps, but not following similar durations of wakefulness. These fi ndings suggest that memory consolidation that occurs during wakefulness is enhanced during sleep.Synaptic plasticity, which refers to structural or functional neural changes in response to stimuli, 2 is thought to be the cellular substrate underlying the processes of memory formation and consolidation.11 Sleep has been found to enhance plasticity in animals, 12 which is consistent with the idea that sleep enhances memory consolidation. In humans, fMRI studies have shown that sleep-dependent learning of a motor skill task is accompanied by changes in multiple brain areas, BRIEF SUMMARYCurrent Knowledge/Study Rationale: Few studies have investigated the impact of hypnotic medication on sleep-dependent memory consolidation. This study compared the effect of differing time of exposure to two hypnotics on the sleep-dependent consolidation of declarative and non-declarative memory. Study Impact: This study contributes to the research surrounding sleep-dependent memory and hypnotics, indicating that hypnotic exposure during most of the night may reduce sleep-dependent memory consolidation; whereas hypnotic exposure only during the second half of the night appears to have no effect.

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Section: Discussionmentioning

confidence: 89%

The Effect of Two Benzodiazepine Receptor Agonist Hypnotics on Sleep-Dependent Memory Consolidation

Hall-Porter

Schweitzer

Eisenstein

et al. 2014

Journal of Clinical Sleep Medicine

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“…This is in comparison with short-acting benzodiazepines that have elimination half-lives around 8-10 h. However, too short a half-life may be a problem for patients that require sleep maintenance therapy. Pharmacokinetic properties of Z-drugs are shown in Table 1; major metabolic pathways are in italics [10,12,[15][16][17][18][19].…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…Of the Major metabolic pathways are in italics. References include [10,12,[15][16][17][18][19] IR immediate-release preparation, ER extended/controlled-release preparation, T max time to maximal concentration (hours), t ½ half-life (hours), CYP cytochrome P450 enzyme Z-drugs, the majority of these events appear to relate to zolpidem though this may merely reflect its higher usage rates or higher doses [7]. Z-drugs have the potential to cause residual effects post-awakening that relate to cognition, memory, parasomnia, and bizarre behavior.…”

Section: Adverse Effectsmentioning

confidence: 99%

The Clinical and Forensic Toxicology of Z-drugs

Gunja

2013

J. Med. Toxicol.

159

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The Z-drugs zolpidem, zopiclone, and zaleplon were hailed as the innovative hypnotics of the new millennium, an improvement to traditional benzodiazepines in the management of insomnia. Increasing reports of adverse events including bizarre behavior and falls in the elderly have prompted calls for caution and regulation. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. Z-drugs exert their effects through increased γ-aminobutyric acid (GABA) transmission at the same GABA-type A receptor as benzodiazepines. Their pharmacokinetics approach those of the ideal hypnotic with rapid onset within 30 min and short half-life (1-7 h). Zopiclone with the longest duration of action has the greatest residual effect, similar to short-acting benzodiazepines. Neuropsychiatric adverse events have been reported with zolpidem including hallucinations, amnesia, and parasomnia. Poisoning with Z-drugs involves predominantly sedation and coma with supportive management being adequate in the majority. Flumazenil has been reported to reverse sedation from all three Z-drugs. Deaths from Z-drugs are rare and more likely to occur with polydrug overdose. Zdrugs can be detected in blood, urine, oral fluid, and postmortem specimens, predominantly with liquid chromatography-mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Zaleplon with its ultra-short half-life has been detected in few clinical or forensic cases possibly due to assay unavailability, low frequency of use, and short window of detection. Though Z-drugs have improved pharmacokinetic profiles, their adverse effects, neuropsychiatric sequelae, and incidence of poisoning and death may prove to be similar to older hypnotics.

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“…An interesting observation with zolpidem was that it did not affect the retrograde part of an individual's memory unlike benzodiazepines but the anterograde memory was seen to be affected. 14,15 It was seen that co-administration with drugs like imipramine, ketoconazole etc. led to increased exposure to zolpidem as these drugs inhibit the CYP3A4 enzyme which metabolizes zolpidem.…”

Section: Zolpidemmentioning

confidence: 99%

Drugs affecting sleep and wakefulness: a review

Amar

2018

Int J Basic Clin Pharmacol

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It was in the second half of the twentieth century that Sleep Medicine was recognized as an immensely respected field of clinical research. As a result, past few decades have seen this field making some giant strides towards a better understanding of the neurochemical mechanisms that regulate the state of sleep and wakefulness. This involves a complex interplay of neuronal systems, neurotransmitters and some special nuclei located in the brain. Major wakefulness promoting nuclei being the orexinergic neurons in the lateral hypothalamic region and the tuberomammillary nucleus (TMN) while the sleep-promoting nucleus being ventrolateral preoptic nucleus (VLPO). Sleep-related complaints are one of the common complaints encountered by the physicians and the psychiatrists. As, long-standing sleep disturbances can have far-reaching implications on an individual’s physical, mental and social wellbeing, the importance of drugs affecting sleep and wakefulness could not be stressed upon anymore. Broadly, the sleep disorders are classified as insomnia, hypersomnia, and parasomnia and the presently available drugs work either by acting on the sleep-promoting GABAergic system like benzodiazepines, barbiturates etc. or by interacting with wakefulness promoting system like histaminergic system, 5- hydroxtryptaminergic system, orexinergic system etc. There are drugs which interact with other mechanisms which modulate arousal, like melatonin receptor agonists which promote sleep and adenosine receptor antagonists which promote wakefulness. This review article tries to have an overview of the available drugs for use in pathological states of sleep and wakefulness with a special emphasis on the commonly prescribed drugs and the recently approved one’s.

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Dynamics and Kinetics of a Modified‐Release Formulation of Zolpidem: Comparison With Immediate‐Release Standard Zolpidem and Placebo

Cited by 55 publications

References 43 publications

The Effect of Two Benzodiazepine Receptor Agonist Hypnotics on Sleep-Dependent Memory Consolidation

The Effect of Two Benzodiazepine Receptor Agonist Hypnotics on Sleep-Dependent Memory Consolidation

The Clinical and Forensic Toxicology of Z-drugs

Drugs affecting sleep and wakefulness: a review

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