Individual Variations in the Elimination Process of Fentanyl in Patients

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著者

    • SERA Shoji
    • 福山大学薬学部 Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
    • GOROMARU Tsuyoshi
    • 福山大学薬学部 Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
    • SAMESHIMA Teruko
    • 鹿児島大学医学部麻酔蘇生学教室 Department of Anesthesiology and Critical Care Medicine, Kagoshima University Faculty of Medicine
    • ODA Toshiyuki
    • 鹿児島大学医学部麻酔蘇生学教室 Department of Anesthesiology and Critical Care Medicine, Kagoshima University Faculty of Medicine

抄録

The quantitative determination of serum fentanyl (FT), urinary FT and its main metabolite, Nor-FT was examined to ascertain the individual variation in the elimination process of FT among 17 patients. The pharmacokinetics of FT was solved from the obtained data using 2-compartment model including the metabolic process. Furthermore, we compared Nor-FT excretion with CYP3A4 activity based on urinary 6β-hydroxycortisol (6β-OHF) and cortisol (F) excretion ratio.<BR> FT and Nor-FT were determined by isotope dilution analysis using deuterium labeled FT (FT-<SUP>2</SUP>H<SUB>19</SUB>) or Nor-FT (Nor-FT-<SUP>2</SUP>H<SUB>10</SUB>) as internal standards. The isotopic fractionation was achieved by a capillary gas chromatograph equipped with a surface ionization detector. The pharmacokinetic parameters were calculated from serum FT concentration time profiles and excreted amount of FT and Nor-FT in urine, using the pharmacokinetic data analysis software, WinNonlin standard Ver. 1.5 (Scientific Consulting). Urinary F and 6β-OHF concentrations were determined by HPLC using fludrocortisone as an internal standard after conversion to fluorescence derivative using 1, 2-diamino-4, 5-methylenedioxybenzene.<BR> The obtained pharmacokinetic parameters showed considerable difference between individuals. The predicted time course for FT and Nor-FT was adapted to FT kinetics. The predicted final excretion rates of FT and Nor-FT were 0.14-15.77% (mean 4.30%) and 7.36-99.38% (mean 55.12%), respectively. The CYP3A4 activity obtained from steroid excretion was not reflected by FT elimination in this study for a low dose of FT (5μg/kg).

収録刊行物

  • 薬物動態 = Xenobiotic metabolism and disposition

    薬物動態 = Xenobiotic metabolism and disposition 15(6), 495-503, 2000-12-01

    日本薬物動態学会

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各種コード

  • NII論文ID(NAID)
    10008416680
  • NII書誌ID(NCID)
    AN10144117
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    09161139
  • データ提供元
    CJP書誌  J-STAGE 
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