Pharmacokinetics of Fentanyl

  • L. E. Mather
  • G. K. Gourlay


The fundamental pharmacokinetic properties of any drug are the rate and extent of distribution in the body and the rate and route(s) of elimination from the body. These, as a rule, are determined after intravenous administration. As reported in a variety of studies using traditional compartment pharmacokinetic methodology over the past 10 years, the fundamental pharmacokinetic properties of fentanyl in adult humans are not complex. On average, these properties consist of an extensive extravascular distribution (total apparent volume of distribution,Vss = 300–400 1/70 kg), a medium to high total body clearance (0.5–1.21/min), and a low renal clearance (urinary excretion <10% dose), and are consistent with the lipophilic tertiary amine chemical structure of fentanyl. It is noteworthy that there is a large variability in the results of different investigations and there may be many reasons for this. Assay differences may account for some of the problems. At the doses used, blood fentanyl concentrations after intravenous bolus are not readily measurable with accuracy by specific chemical methods over a sufficient range, and immunoassay methods still leave residual concerns about specificity. Undoubtedly, some of the variability in reported pharmacokinetics of fentanyl also derives from differences in the samples assayed (e.g., arterial or venous blood, plasma or serum; and drug sorption), differences in the physiological status of the subjects (e.g., age, pathology, binding proteins, concomitant drugs, anesthesia and surgery) and differences in the mode of fentanyl administration (e.g., bolus, infusion). With some exceptions, these variables have not been examined systematically, but it is clear from first principles that each could be significant.


High Performance Liquid Chromatography Epidural Administration Fentanyl Concentration Fentanyl Citrate Oral Transmucosal Fentanyl Citrate 
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© Springer-Verlag Berlin Heidelberg 1991

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  • L. E. Mather
  • G. K. Gourlay

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