論文

2020年6月

Utilizing physiologically based pharmacokinetic modeling to predict theoretically conceivable extreme elevation of serum flecainide concentration in an anuric hemodialysis patient with cirrhosis

European journal of clinical pharmacology
  • Doki, Kosuke
  • ,
  • Kuga, Keisuke
  • ,
  • Aonuma, Kazutaka
  • ,
  • Ieda, Masaki
  • ,
  • Homma, Masato

76
6
開始ページ
821
終了ページ
831
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00228-020-02861-9
出版者・発行元
SPRINGER HEIDELBERG

[PURPOSE] Higher drug concentrations in complex clinical scenarios in which multiple factors such as drug-drug interactions (DDIs) and comorbidities are simultaneously present are not necessarily rationalized in prospective clinical studies. Physiologically based pharmacokinetic (PBPK) modeling and simulation of the anti-arrhythmic drug flecainide, as an example, were utilized to quantitatively rationalize the higher flecainide concentration in a complex clinical case involving end-stage renal disease (ESRD), cirrhosis, and the co-administration of mexiletine, a CYP1A2 inhibitor.
[METHODS] The developed flecainide PBPK model was used to evaluate the DDI effect (as measured by AUC ratio before and after inhibition) of mexiletine and the combined disease effects of ESRD and cirrhosis on flecainide exposure.
[RESULTS] The predicted DDI effect of mexiletine was negligible or weak in anuric hemodialysis with cirrhosis population (mean [5th/95th percentiles], 1.23 [0.97-1.67]), although it was negligible in healthy volunteers (1.03 [1.02-1.05]). The predicted flecainide concentrations after multiple flecainide doses (50 mg BID) in the anuric hemodialysis with cirrhosis population were c

リンク情報
DOI
https://doi.org/10.1007/s00228-020-02861-9
ID情報
  • DOI : 10.1007/s00228-020-02861-9
  • ISSN : 1432-1041

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