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Modeling sleep data...
Modeling sleep data for a new drug in development using Markov mixed-effects models
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- Kjellsson, Maria C. (författare)
- Uppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi,Farmakometri
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Ouellet, Daniele (författare)
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Corrigan, Brian (författare)
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- Karlsson, Mats O. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
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(creator_code:org_t)
- 2011-06-17
- 2011
- Engelska.
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 28:10, s. 2610-2627
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- To characterize the time-course of sleep in insomnia patients as well as placebo and concentration-effect relationships of two hypnotic compounds, PD 0200390 and zolpidem, using an accelerated model-building strategy based on mixed-effects Markov models. Data were obtained in a phase II study with the drugs. Sleep stages were recorded during eight hours of sleep for two nights per treatment for the five treatments. First-order Markov models were developed for one transition at a time in a sequential manner; first a baseline model, followed by placebo and lastly the drug models. To accelerate the process, predefined models were selected based on a priori knowledge of sleep, including inter-subject and inter-occasion variability. Baseline sleep was described using piece-wise linear models, depending on time of night and duration of sleep stage. Placebo affected light sleep stages; drugs also affected slow-wave sleep. Administering PD 0200390 30 min earlier than standard dosing was shown through simulations to reduce latency to persistent sleep by 40%. The proposed accelerated model-building strategy resulted in a model well describing sleep patterns of insomnia patients with and without treatments.
Nyckelord
- Markov model
- NONMEM
- pharmacodynamics
- polysomnography
- population analysis
- sleep
- transition model
- zolpidem
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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