Population pharmacokinetics of fentanyl in healthy volunteers.
The authors compared the population pharmacokinetics of fentanyl using a standard individualized modeling (SIM) approach versus that of a nonparametric expectation maximization (NPEM) approach. The pharmacokinetic properties of fentanyl administered as a single 5 ug/kg intravenous infusion were evaluated in 18 healthy volunteers by use of SIM as well as with NPEM. NPEM-derived parameters were a total body clearance of 2.12 +/- 0.28 L/kg/h, distributional clearance of 8.43 +/- 4.58 L/kg/h, central volume of distribution of 1.22 +/- 0.21 L/kg, and peripheral volume of distribution of 1.81 +/- 1.47 L/kg. Identified parameter values from the modeling methods resulted in virtually identical simulated profiles; this finding was confirmed when median values noted were not statistically significantly different between modeling methods (SIM or NPEM). However, the NPEM algorithm uniquely identified a greater distributional clearance in the elderly population and also illustrated a profile with at least 10% of the study population having a very high clearance of fentanyl. This finding may affect the therapeutic use of fentanyl. NPEM allows for a more informative global representation of a drug's pharmacokinetics.
Ariano
R E
RE
Department of Pharmacy, St. Boniface General Hospital.
Duke
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PC
Sitar
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DS
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D005260:Female; D005283:Fentanyl / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009294:Narcotics / Q000097:blood / Q000493:pharmacokinetics*; D011336:Probability; D017678:Sex Distribution
D009294:Narcotics; D005283:Fentanyl