Individual Variations in the Elimination Process of Fentanyl in Patients

Access this Article

Search this Article

Author(s)

    • 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

Abstract

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).

Journal

  • Drug Metabolism and Pharmacokinetics

    Drug Metabolism and Pharmacokinetics 15(6), 495-503, 2000-12-01

    The Japanese Society for the Study of Xenobiotics

References:  36

Codes

  • NII Article ID (NAID)
    10008416680
  • NII NACSIS-CAT ID (NCID)
    AN10144117
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    09161139
  • Data Source
    CJP  J-STAGE 
Page Top