uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Analysis of exposure-response of CI-945 in patients with epilepsy: application of novel mixed hidden Markov modeling methodology
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Pharmacometrics)
Show others and affiliations
2012 (English)In: Journal of Pharmacokinetics and Pharmacodynamics, ISSN 1567-567X, E-ISSN 1573-8744, Vol. 39, no 3, 263-271 p.Article in journal (Refereed) Published
Abstract [en]

We propose to describe exposure-response relationship of an antiepileptic agent, using mixed hidden Markov modeling methodology, to reveal additional insights in the mode of the drug action which the novel approach offers. Daily seizure frequency data from six clinical studies including patients who received gabapentin were available for the analysis. In the model, seizure frequencies are governed by underlying unobserved disease activity states. Individual neighbouring states are dependent, like in reality and they exhibit their own dynamics with patients transitioning between low and high disease states, according to a set of transition probabilities. Our methodology enables estimation of unobserved disease dynamics and daily seizure frequencies in all disease states. Additional modes of drug action are achievable: gabapentin may influence both daily seizure frequencies and disease state dynamics. Gabapentin significantly reduced seizure frequencies in both disease activity states; however it did not significatively affect disease dynamics. Mixed hidden Markov modeling is able to mimic dynamics of seizure frequencies very well. It offers novel insights into understanding disease dynamics in epilepsy and gabapentin mode of action.

Place, publisher, year, edition, pages
2012. Vol. 39, no 3, 263-271 p.
Keyword [en]
Mixed hidden Markov model, Epilepsy, CI-945, Maximum likelihood estimation, Monolix
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-176817DOI: 10.1007/s10928-012-9248-2ISI: 000304617500004OAI: oai:DiVA.org:uu-176817DiVA: diva2:537725
Available from: 2012-06-27 Created: 2012-06-26 Last updated: 2017-12-07Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Karlsson, Mats O.

Search in DiVA

By author/editor
Karlsson, Mats O.
By organisation
Department of Pharmaceutical Biosciences
In the same journal
Journal of Pharmacokinetics and Pharmacodynamics
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 368 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf