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
Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Farmakometri)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Farmakometri)
Show others and affiliations
2008 (English)In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 84, no 1, 52-62 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to develop a model describing the carbamazepine autoinduction and the carbamazepine-mediated induction of CYP3A4, CYP1A2, and P-glycoprotein. Seven healthy volunteers were dosed with carbamazepine over 16 consecutive days. The CYP3A4, CYP1A2, and P-glycoprotein activities were assessed, using midazolam, caffeine, and digoxin as probe substrates, on 12 occasions, covering the preinduced state and the onset and termination of the induction process. The data were evaluated using a mechanistic pharmacokinetic approach in NONMEM. The induction processes were described using turnover models, with carbamazepine and carbamazepine-10,11-epoxide as the driving force of the induction. The half-lives of CYP3A4 and CYP1A2 were estimated to be 70 and 105 h, respectively. P-glycoprotein was not affected by the carbamazepine treatment. The possibility of modeling the pharmacodynamics of enzyme induction using a turnover model was illustrated, and the time course of the process was estimated with good precision.

Place, publisher, year, edition, pages
2008. Vol. 84, no 1, 52-62 p.
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-102615DOI: 10.1038/sj.clpt.6100431ISI: 000256837400011PubMedID: 17971810OAI: oai:DiVA.org:uu-102615DiVA: diva2:216519
Available from: 2009-05-09 Created: 2009-05-09 Last updated: 2017-12-13Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Department of Pharmaceutical BiosciencesClinical Pharmacology
In the same journal
Clinical Pharmacology and Therapeutics
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 448 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