2000 Volume 15 Issue 6 Pages 495-503
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.
FT and Nor-FT were determined by isotope dilution analysis using deuterium labeled FT (FT-2H19) or Nor-FT (Nor-FT-2H10) 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.
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).
