scholarly journals Pharmacotherapy of Insomnia: Focus on Zolpidem Extended Release

2009 ◽  
Vol 1 ◽  
pp. CMT.S2040 ◽  
Author(s):  
J.M. Monti ◽  
D. Warren Spence ◽  
S.R. Pandi-Perumal ◽  
Salomon Z. Langer ◽  
R. Hardeland
Keyword(s):  
Extended Release ◽  
Sleep Onset ◽  
Immediate Release ◽  
Sleep Time ◽  
After Effects ◽  
Sleep Maintenance ◽  
Acting Agent ◽  
Relative Selectivity ◽  
Hepatic Cytochrome ◽  
Methyl Phenyl

The imidazopyridine drug zolpidem ( N,N,6-trimethyl-2[4-methyl-phenyl]imidazo[1,2-a]pyridine-3-acetamide) is a sedative/hypnotic with relative selectivity for α1 subunits of the GABAA receptor/chloride channel complex. Because of this selectivity and regional receptor distribution, zolpidem is less generalized in its CNS depressive actions than benzodiazepines and largely devoid of their major, undesired side- and after-effects, at recommended doses. Zolpidem is rapidly taken up and distributed, binds extensively to plasma proteins, and is readily inactivated by hepatic cytochrome P450 monooxygenases, especially CYP3A4. Zolpidem is thus a rapidly acting agent which provides effective facilitation of sleep onset. However, plasma levels of the immediate release (IR) formulation frequently decline too quickly for effective sleep maintenance. To address this problem zolpidem extended release (ER) has been developed. At age-specific dosages, it increases, in middle-aged and elderly patients, total sleep time and reduces the number of nocturnal awakenings. Both zolpidem IR and ER have favorable toxicological profiles. Adverse effects are moderate, frequently in the incidence range of placebos, and certainly less frequent and severe than those of benzodiazepines. Zolpidem IR and ER are practically devoid of next-day hangover effects and only infrequently cause rebound insomnia of usually short duration. Both variants of zolpidem have a limited potential for dependence and abuse.

scholarly journals A study on sleep apnea in patients with abnormal sewda type of depression

2020 ◽  
pp. 1-8
Author(s):  
Aman Gul ◽  
Nassirhadjy Memtily ◽  
Pirdun Mijit ◽  
Palidan Wushuer ◽  
Ainiwaer Talifu ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Sleep Onset ◽  
Sleep Time ◽  
Sleep Efficiency ◽  
Control Group ◽  
Poor Sleep ◽  
Sleep Structure ◽  
Maintenance Rate ◽  
Sleep Maintenance ◽  
Insomnia Symptoms

Objective: To preliminarily investigate the clinical features and PSG in abnormal sewda-type depressive insomnia. Methods: A total of 127 abnormal sewda-type depressive insomnia patients were evaluated with overnight PSG, and 32 normal participants were compared. Results: Patients with abnormal sewda-type depressive insomnia were compared with the control group; the sleep symptoms showed a long incubation period of sleep, low sleep maintenance rate, low sleep efficiency and poor sleep quality as well as daytime dysfunction. At process and continuity of sleep: Total sleep time, sleep efficiency, sleep maintenance rate in abnormal sewda-type depressive insomnia group were shorter than the control group. Wake after sleep onset, and sleep latency were longer than the control group. At sleep structure: N1 ratio and N2 ratio in depressive insomnia group were longer than the control group, N3 ratio and REM sleep ratio shorter than the control group. At REM index: REM latency, REM cycles, and REM sleep time were shorter than the control group. Conclusion: Insomnia symptoms in abnormal sewda-type depression comorbid insomnia patients were similar to the ordinary insomnia patients. The PSG characteristics had significant changes in sleep process, sleep structure and REM indicators. The severity of the abnormal sewda-type depression was closely related to REM indicators. Change of REM sleep characteristics may be the specificity, and these could be taken as reference in diagnosis and identification of abnormal sewda-type depressive insomnia.

Effect on Primary Sleep Disorders When Children With ADHD Are Administered Guanfacine Extended Release

2014 ◽  
Vol 22 (1) ◽  
pp. 14-24 ◽  
Author(s):  
Thomas A. Rugino
Keyword(s):  
Extended Release ◽  
Slow Wave Sleep ◽  
Sleep Problems ◽  
Sleep Onset ◽  
Sleep Time ◽  
Outcome Variable ◽  
Controlled Study ◽  
Double Blind ◽  
Children With Adhd ◽  
Time Awake

Objective: To evaluate children with ADHD and sleep problems with polysomnography (PSG) after guanfacine extended-release (GXR) administration. Method: Double-blind, randomized, placebo-controlled study was terminated early due to treatment-emergent concerns after enrolling 29 children aged 6 to 12 years. After >4 weeks dose adjustment and >1 week dose stabilization, 11 children received GXR and 16 controls underwent analyses with PSG. Results: Although GXR improved ADHD symptoms, the primary outcome variable, total sleep time, was shorter in contrast to placebo (−57.32, SD = 89.17 vs. +31.32, SD = 59.54 min, p = .005). Increased time awake after sleep onset per hour of sleep was the primary factor for the reduction. Although rapid eye movement (REM), non-REM, and N3/slow wave sleep times were reduced, these were proportional to the overall sleep reduction. Sedation was common with GXR (73% vs. 6%). Conclusion: Morning-administered GXR resulted in decreased sleep and may contribute to sedation.

631 Sleep SMART in Adolescents with Neurodevelopmental Disorders

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A247-A248
Author(s):  
Alyson Hanish ◽  
Abbey Jo Klein ◽  
Therese Mathews ◽  
Ann Berger ◽  
Kevin Kupzyk ◽  
...  
Keyword(s):  
Sleep Disturbance ◽  
Neurodevelopmental Disorders ◽  
Sleep Disturbances ◽  
Immediate Release ◽  
Sleep Time ◽  
Normative Values ◽  
Exogenous Melatonin ◽  
Contingency Contracting ◽  
Sleep Questionnaires ◽  
The Impact

Abstract Introduction: Introduction Sleep disturbances are common in adolescents with neurodevelopmental disorders (NDDs). Inclusion of vulnerable populations such as adolescents with NDDs into sleep intervention efforts is essential as they are at high-risk for poor physical/mental health outcomes. The objective of this study is to pilot a sequential, multiple assignment, randomized trial (SMART) design to compare the impact of a sequence of sleep interventions, based on treatment response, to optimize sleep health in adolescents with NDDs. Methods: Methods Recruitment began June 2019 using convenience sampling. The SMART pilot feasibility study includes 1-week of baseline sleep data, and two 4-week periods of a sleep intervention (9-week total study enrollment). Interventions include exogenous melatonin, The Bedtime Bank, and their combination. Exogenous melatonin (liquid, immediate release, 3mg) is administered 30 minutes before bedtime. The Bedtime Bank, a behavioral sleep intervention, is based upon contingency contracting that relies on a credit- or debt-based system to hold adolescents accountable for maintaining a consistent bedtime. At baseline participants completed demographics, PROMIS pediatric sleep questionnaires, the Cleveland Adolescent Sleepiness Questionnaire (CASQ), salivary & urinary endogenous melatonin measurement, and one week of actigraphy. Upon enrollment, participants were randomly assigned to either melatonin or The Bedtime Bank. Participants who respond (nightly increase in total sleep time (TST) ≥18 minutes) remain on the assigned intervention; if non-responsive participants are re-randomized to a different sleep intervention or combination. Results: Results At baseline, participants (n=29, aged 10–18 years) had an average TST of 7 hours 11 minutes. PROMIS Sleep Disturbance (M=64.3, SE=2.5), PROMIS Sleep-Related Impairment scores (M=58.9, SE=2.2), and CASQ scores (M=40.0, SD= 10.5) were higher than reported normative values. Salivary DLMO & urinary 6-sulfatoyxmelatonin analysis is ongoing. For participants who completed the full 9-week trial, nearly 30% (n=7/24) were responsive (increased baseline TST ≥18 minutes) to one of the 4-week interventions. Conclusion: Conclusion Baseline data of the enrolled participants demonstrates poor indicators of TST, sleep disturbance, and sleep related impairment. Preliminary results of this SMART indicate some adolescents are responsive to sleep interventions aimed to improve their TST. Support (if any) Support: This clinical trial is funded by the National Institute of Nursing Research, National Institutes of Health (1K01NR017465-01A1).

scholarly journals 0004 TS-142: A Novel and Potent Dual Orexin Receptor Antagonist with Sleep-Promoting Effects in Rats

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A2-A2
Author(s):  
D Kambe ◽  
H Hikichi ◽  
Y Tokumaru ◽  
M Ohmichi ◽  
Y Konno ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Half Life ◽  
Sleep Onset ◽  
Sleep Time ◽  
Sleep Onset Latency ◽  
Orexin A ◽  
Pharmacokinetic Profiles ◽  
Orexin Receptors ◽  
Elimination Half ◽  
Emg Electrodes

Abstract Introduction The orexin system plays a pivotal role in regulating sleep and wakefulness, thus, orexin receptors (OX1 and OX2 receptors) have gained much attention as promising therapeutic targets for the treatment of insomnia. We synthesized a novel and potent dual orexin receptor antagonist (DORA), ORN0829 (investigation code name as TS-142), which was designed to have short-acting effects. Here we report pharmacological and pharmacokinetic profiles of ORN0829 in rats. Methods The antagonistic activities of ORN0829 were assessed using calcium mobilization assays. Ala-orexin A-induced [Ca2+]i response was measured with CHO-K1 cells stably expressing human/rat orexin receptor. Rats implanted the EEG/EMG electrodes were orally administrated ORN0829 at doses of 1, 3 or 10 mg/kg at the dark onset and sleep-wake stages were inspected visually. In addition, pharmacokinetic profiles of ORN0829 were investigated in rats. Results ORN0829 inhibited Ala-orexin A-increased [Ca2+]i response with a Kb of 0.67/0.44 nmol/L (for human/rat OX1 receptor), and with a Kb of 0.84/0.80 nmol/L (for human/rat OX2 receptor), respectively, indicating that ORN0829 is a potent DORA with no species differences. ORN0829 dose-dependently increased total sleep time and reduced sleep onset latency at doses of 1, 3 and 10 mg/kg. Importantly, the ORN0829 levels in plasma and cerebrospinal fluid rapidly reached a maximum concentration, and decreased with an elimination half-life of less than 1 h. Conclusion The present study indicates that ORN0829 is a novel and potent DORA with sleep-promoting effects, and that it exhibits ideal pharmacokinetic profiles (rapid absorption and short half-life) in rats. A phase 2a study of TS-142 using patients with insomnia has been completed, which is presented in a separate poster. Support Taisho Pharmaceutical. Co., Ltd.

scholarly journals 1253 Multiple sleep onset REM episodes in middle age woman with excessive daytime sleepiness – Is this automatically assumed narcolepsy?

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A477-A477
Author(s):  
Kamal Patel ◽  
Bianca J Lang
Keyword(s):  
Daytime Sleepiness ◽  
Sleep Latency ◽  
Sleep Onset ◽  
Sleep Time ◽  
Multiple Sleep Latency Test ◽  
Sleep Onset Latency ◽  
Onset Latency ◽  
Obstructive Sleep ◽  
Falling Asleep ◽  
Multiple Sleep Latency

Abstract Introduction Presence of sleep onset REM episodes often raises concerns of narcolepsy. However other conditions have shown to have presence of sleep on REM episodes which include but not limited to obstructive sleep apnea, sleep wake schedule disturbance, alcoholism, neurodegenerative disorders, depression and anxiety Report of Case Here we present a case of 30 year old female with history of asthma, patent foraman ovale, migraine headache, and anxiety who presented with daytime sleepiness, falling asleep while at work, occasional scheduled naps, non-restorative sleep, sleep paralysis, and hypnopompic hallucination. Pertinent physical exam included; mallampati score of 4/4, retrognathia, high arched hard palate, crowded posterior oropharynx. She had a score of 16 on Epworth sleepiness scale. Patient previously had multiple sleep latency test at outside facility which revealed 4/5 SOREM, with mean sleep onset latency of 11.5 minutes. She however was diagnosed with narcolepsy and tried on modafinil which she failed to tolerate. She was tried on sertraline as well which was discontinued due to lack of benefit. She had repeat multiple sleep latency test work up which revealed 2/5 SOREM, with mean sleep onset latency was 13.1 minutes. Her overnight polysomnogram prior to repeat MSLT showed SOREM with sleep onset latency of 10 minutes. Actigraphy showed consistent sleep pattern overall with sufficient sleep time but was taking hydroxyzine and herbal medication. Patient did not meet criteria for hypersomnolence disorder and sleep disordered breathing. Conclusion There is possibility her medication may have played pivotal role with her daytime symptoms. We also emphasize SOREMs can be present in other disorders such as anxiety in this case and not solely in narcolepsy

scholarly journals The Cycle of Daily Stress and Sleep: Sleep Measurement Matters

2020 ◽  
Author(s):  
Danica C Slavish ◽  
Justin Asbee ◽  
Kirti Veeramachaneni ◽  
Brett A Messman ◽  
Bella Scott ◽  
...  
Keyword(s):  
Sleep Disturbances ◽  
Multilevel Models ◽  
Single Channel ◽  
Sleep Onset ◽  
Sleep Time ◽  
Sleep Diary ◽  
Sleep Onset Latency ◽  
Daily Stress ◽  
Sleep Diaries ◽  
Sleep Measurement

Abstract Background Disturbed sleep can be a cause and a consequence of elevated stress. Yet intensive longitudinal studies have revealed that sleep assessed via diaries and actigraphy is inconsistently associated with daily stress. Purpose We expanded this research by examining daily associations between sleep and stress using a threefold approach to assess sleep: sleep diaries, actigraphy, and ambulatory single-channel electroencephalography (EEG). Methods Participants were 80 adults (mean age = 32.65 years, 63% female) who completed 7 days of stressor and sleep assessments. Multilevel models were used to examine bidirectional associations between occurrence and severity of daily stress with diary-, actigraphy-, and EEG-determined sleep parameters (e.g., total sleep time [TST], sleep efficiency, and sleep onset latency, and wake after sleep onset [WASO]). Results Participants reported at least one stressor 37% of days. Days with a stressor were associated with a 14.4-min reduction in actigraphy-determined TST (β = −0.24, p = 0.030), but not with other actigraphy, diary, or EEG sleep measures. Nights with greater sleep diary-determined WASO were associated with greater next-day stressor severity (β = 0.01, p = 0.026); no other diary, actigraphy, or EEG sleep measures were associated with next-day stressor occurrence or severity. Conclusions Daily stress and sleep disturbances occurred in a bidirectional fashion, though specific results varied by sleep measurement technique and sleep parameter. Together, our results highlight that the type of sleep measurement matters for examining associations with daily stress. We urge future researchers to treat sleep diaries, actigraphy, and EEG as complementary—not redundant—sleep measurement approaches.

scholarly journals Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

2016 ◽  
Vol 60 (4) ◽  
pp. 2492-2498 ◽  
Author(s):  
Marcelo Gomes Davanço ◽  
Michel Leandro Campos ◽  
Talita Atanazio Rosa ◽  
Elias Carvalho Padilha ◽  
Alejandro Henao Alzate ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Extended Release ◽  
Hydroxypropyl Methylcellulose ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Success ◽  
Preclinical Pharmacokinetics ◽  
Bioavailability Study

ABSTRACTBenznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.

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