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Pharmacodynamics of...
Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin
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- Magnusson, M O (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
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- Dahl, M-L (författare)
- Uppsala universitet,Klinisk farmakologi
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Cederberg, J (författare)
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- Karlsson, M O (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
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- Sandström, R (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
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(creator_code:org_t)
- 2007-10-31
- 2008
- Engelska.
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 84:1, s. 52-62
- 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
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- PHARMACY
- FARMACI
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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