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Absorptive Kinetics of Transdermal Fentanyl. Robert Leonard, PharmD candidate University of Florida College of Pharmacy. Overview. Rationale Barriers TTS-fentanyl Pharmacokinetics Studies of pharmacokinetic variability. Rationale. Continuous infusion Noninvasive nature

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absorptive kinetics of transdermal fentanyl

Absorptive Kinetics of Transdermal Fentanyl

Robert Leonard, PharmD candidate

University of Florida

College of Pharmacy

overview
Overview
  • Rationale
  • Barriers
  • TTS-fentanyl
  • Pharmacokinetics
  • Studies of pharmacokinetic variability
rationale
Rationale
  • Continuous infusion
  • Noninvasive nature
  • Special populations
    • Protracted vomiting
    • Dysphagia
  • Less frequent dosing
barriers
Barriers
  • Epidermal microflora
  • Stratum corneum
  • Subcutaneous vasculature
  • Physicochemical properties
    • MW
    • Lipophilicity
kinetics
Kinetics
  • Absorption
    • F = 0.92
    • Protein binding = 79 - 97%
    • Tmax = 35 hours
  • Distribution
    • Vd = 3 – 8 L/kg
  • Metabolism
    • CYP3A4
    • Major: norfentanyl
    • Minor: hydroxyfentanyl, hydroxynorfentanyl, despropionylfentanyl
kinetics2
Kinetics
  • Elimination
    • Cl = 34.2 – 52.8L/hr
    • T1/2 = 17hrs (after removal)
study
Study
  • Solassol I, Caumette L, Bressolle F, et al. “Inter- and intra-individual variation in transdermal fentanyl absorption in cancer pain patients.” Oncology Reports 14:1029-1036, 2005.
absorption kinetics2
Absorption Kinetics

125 mcg/hr

175 mcg/hr

100 mcg/hr

results
Results
  • Significant findings (P < 0.05)
    • Age: <65, 65-75, >75
      • P = 0.030
    • Primary cancer location: head and neck, GI, GU, Lung, Brest, others
      • P = 0.006
  • Findings approaching significance (P ≤ 0.06)
    • Occlusive bandage: yes, no
      • P = 0.060
    • Temperature: <38, 38-40, >40
      • P = 0.051
limitations
Limitations
  • Indirect assay
study1
Study
  • Ashburn MA, Ogden LL, Zhang J, et al. “The pharmacokinetics of transdermal fentanyl delivered with and without controlled heat.” The Journal of Pain 4: 291-297, 2003.
clinical pearls
Clinical Pearls
  • Avoid cutting patches.
  • Avoid occlusive bandages.
  • Avoid heat.
  • Dose according to patient response.
  • Sustained release after removal.
references
References

Ashburn MA, Ogden LL, Zhang J, et al. “The pharmacokinetics of transdermal fentanyl delivered with and without controlled heat.” The Journal of Pain 4: 291-297, 2003.

Grond S, Radbruch L, Lehmann K. “Clinical pharmacokinetics of transdermal opioids: Focus on transdermal fentanyl.” Clinical Pharmacokinetics 38: 59-89, 2000.

Muijsers RB, Wagstaff AJ. “Transdermal fentanyl: An updated review of its pharmacological properties and therapeutic efficacy in chronic cancer pain control.” Drugs 61:2289-2307, 2001.

Solassol I, Caumette L, Bressolle F, et al. “Inter- and intra-individual variation in transdermal fentanyl absorption in cancer pain patients.” Oncology Reports 14:1029-1036, 2005.

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