ArticleJournal of pharmacokinetics and pharmacodynamics2011
A hidden Markov model to assess drug-induced sleep fragmentation in the telemetered rat.
Article in Journal of pharmacokinetics and pharmacodynamics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- A tutorial on pharmacometric Markov models.CPT: pharmacometrics & systems pharmacology · 2025Article
- A hidden Markov modeling approach combining objective measure of activity and subjective measure of self-reported sleep to estimate the sleep-wake cycle.Journal of applied statistics · 2024Article
- Handling underlying discrete variables with bivariate mixed hidden Markov models in NONMEM.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Pharmacometrics models with hidden Markovian dynamics.Journal of pharmacokinetics and pharmacodynamics · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug-induced sleep fragmentation can cause sleep disturbances either via their intended pharmacological action or as a side effect. Examples of disturbances include excessive daytime sleepiness, insomnia and nightmares. Developing drugs without these side effects requires insight into the mechanisms leading to sleep disturbance. The characterization of the circadian sleep pattern by EEG following drug exposure has improved our understanding of these mechanisms and their translatability across species. The EEG shows frequent transitions between specific sleep states leading to multiple correlated sojourns in these states. We have developed a Markov model to consider the high correlation in the data and quantitatively compared sleep disturbance in telemetered rats induced by methylphenidate, which is known to disturb sleep, and of a new chemical entity (NCE). It was assumed that these drugs could either accelerate or decelerate the transitions between the sleep states. The difference in sleep disturbance of methylphenidate and the NCE were quantitated and different mechanisms of action on rebound sleep were identified. The estimated effect showed that both compounds induce sleep fragmentation with methylphenidate being fivefold more potent compared to the NCE.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.