A new sublingual formulation of zolpidem for the treatment of sleep-onset insomnia

Staner, Luc; Danjou, Philippe; Luthringer, R.

doi:10.1586/ern.11.197

Cited by 10 publications

(4 citation statements)

References 103 publications

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“…Thereafter, the fitted parameter values were transferred to PK‐Sim, and the specific intestinal permeability was fitted to pharmacokinetic data in the fasted state from multiple clinical studies 27,28,31–33 . Another independent set of clinical data not used during parameter optimization was thereafter used to evaluate the adult PBPK model 34–45 …”

Section: Methodsmentioning

confidence: 99%

Evaluation of Physiologically Based Pharmacokinetic Models to Predict the Absorption of BCS Class I Drugs in Different Pediatric Age Groups

Liu

Anker

Burckart

et al. 2021

The Journal of Clinical Pharma

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Age‐related changes in many parameters affecting drug absorption remain poorly characterized. The objective of this study was to apply physiologically based pharmacokinetic (PBPK) models in pediatric patients to investigate the absorption and pharmacokinetics of 4 drugs belonging to the Biopharmaceutics Classification System (BCS) class I administered as oral liquid formulations. Pediatric PBPK models built with PK‐Sim/MoBi were used to predict the pharmacokinetics of acetaminophen, emtricitabine, theophylline, and zolpidem in different pediatric populations. The model performance for predicting drug absorption and pharmacokinetics was assessed by comparing the predicted absorption profile with the deconvoluted dose fraction absorbed over time and predicted with observed plasma concentration‐time profiles. Sensitivity analyses were performed to analyze the effects of changes in relevant input parameters on the model output. Overall, most pharmacokinetic parameters were predicted within a 2‐fold error range. The absorption profiles were generally reasonably predicted, but relatively large differences were observed for acetaminophen. Sensitivity analyses showed that the predicted absorption profile was most sensitive to changes in the gastric emptying time (GET) and the specific intestinal permeability. The drug's solubility played only a minor role. These findings confirm that gastric emptying time, more than intestinal permeability or solubility, is a key factor affecting BCS class I drug absorption in children. As gastric emptying time is prolonged in the fed state, a better understanding of the interplay between food intake and gastric emptying time in children is needed, especially in the very young in whom the (semi)fed condition is the prevailing prandial state, and hence prolonged gastric emptying time seems more plausible than the fasting state.

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Section: Methodsmentioning

confidence: 99%

Evaluation of Physiologically Based Pharmacokinetic Models to Predict the Absorption of BCS Class I Drugs in Different Pediatric Age Groups

Liu

Anker

Burckart

et al. 2021

The Journal of Clinical Pharma

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“…Thus, fast-acting low-dose zolpidem is associated with a rapid onset of short-term (four hours) sedation. This formulation does not appear to accumulate in the plasma, even after long-term administration [23]. …”

Section: Pharmacokinetics Of Sublingual Formulationsmentioning

confidence: 99%

Fast-Acting Sublingual Zolpidem for Middle-of-the-Night Wakefulness

et al. 2014

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Sleep disorders (somnipathies) are conditions characterized by disruptions of sleep quality or of sleep pattern. They can involve difficulty falling asleep (prolonged sleep onset latency), difficulty staying asleep (disturbance of sleep maintenance), sleep of poor quality (unrefreshing), or combinations of these and can lead to poor health and quality of life problems. A subtype of sleep-maintenance insomnia is middle-of-the-night wakefulness, a relatively common occurrence. Zolpidem, a nonbenzodiazepine benzodiazepine receptor agonist, allosterically modulates an ion channel and increases the influx of Cl−, thereby dampening the effect of excitatory (sleep disrupting) input. Recently, product label changes to some zolpidem containing products have been implemented by the FDA in order to reduce the risk associated with their morning after residual side effects. A new formulation of zolpidem tartrate (Intermezzo) sublingual tablet, an approved product indicated exclusively for the treatment of middle-of-the-night wakefulness and difficulty returning to sleep, did not have its label changed. We present a short summary of its basic science and clinical attributes in light of the recent regulatory changes for zolpidem products.

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“…1 It is characterized by one or more of the following subjective complaints: a) a sleep onset latency of over 30 min, b) nightly sleep duration of less than 6 h, and/or c) waking too early and being unable to return to sleep (also referred to as unrefreshed sleep). 2 Studies conducted in the general population indicate that adults experience more of these symptoms, while the National Sleep Foundation's Sleep in America Poll 2005 found that more than 50% of Americans were Declaration of Interests: The authors certify that they have no commercial or associative interest that represents a conflict of interest in connection with the manuscript.…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo evaluation of nano-based films for buccal delivery of zolpidem

Al‐Dhubiab

2016

Braz. oral res.

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In vitro and in vivo evaluation of nano-based films for buccal delivery of zolpidem Abstract: Insomnia is becoming increasingly prevalent in the world general population. Therapies used by patients include over-the-counter therapies, herbal and dietary supplements, and pharmacological or nonpharmacological treatments. Among these, zolpidem is a pharmacological treatment popularly used for insomnia. Zolpidem is well tolerated and especially efficacious for initiation of sleep, and therefore is effective for the treatment of sleep-onset insomnia. The purpose of the present study was to design and evaluate zolpidem nanoparticle-impregnated buccal films to prolong the duration of its action. Zolpidem nanospheres were prepared by double emulsion solvent evaporation and then loaded into buccoadhesive films (Z1-Z4) comprised of different concentrations of HPMC K100, Eudragit ® RL 100, and carbopol 974P. The prepared films were characterized for physicomechanical properties, mucoadhesion, percent hydration, in vitro drug release, ex vivo permeation, and in vivo studies. In vitro drug release was found to depend upon film composition. Ex vivo studies showed that film Z4 had the highest flux. In vivo studies revealed that administration of zolpidem nanosphere-impregnated film enhanced absorption of the drug (p < 0.0001), with a higher peak plasma concentration (52.54 ± 8.22 ng/mL) and area under the curve from time 0 to α (236.00 ± 39.51 ng.h/mL) than oral administration. The increase in time taken to reach the maximum drug concentration (1.5 h) further signifies the potential of these films to provide prolonged drug release. Given these promising results, we concluded that these buccal films could be an alternative route for effective zolpidem delivery.

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A new sublingual formulation of zolpidem for the treatment of sleep-onset insomnia

Cited by 10 publications

References 103 publications

Evaluation of Physiologically Based Pharmacokinetic Models to Predict the Absorption of BCS Class I Drugs in Different Pediatric Age Groups

Evaluation of Physiologically Based Pharmacokinetic Models to Predict the Absorption of BCS Class I Drugs in Different Pediatric Age Groups

Fast-Acting Sublingual Zolpidem for Middle-of-the-Night Wakefulness

In vitro and in vivo evaluation of nano-based films for buccal delivery of zolpidem

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