Absorptive Kinetics of Transdermal Fentanyl

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Absorptive Kinetics of Transdermal Fentanyl

• Robert Leonard, PharmD candidate
• University of Florida
• College of Pharmacy

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Overview

• Rationale
• Barriers
• TTS-fentanyl
• Pharmacokinetics
• Studies of pharmacokinetic variability

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Rationale

• Continuous infusion
• Noninvasive nature
• Special populations
• Protracted vomiting
• Dysphagia
• Less frequent dosing

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Barriers

• Epidermal microflora
• Stratum corneum
• Subcutaneous vasculature
• Physicochemical properties
• MW
• Lipophilicity

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TTS-fentanyl
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Pharmacokinetics
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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

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Kinetics
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Kinetics

• Elimination
• Cl 34.2 52.8L/hr
• T1/2 17hrs (after removal)

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Study

• Solassol I, Caumette L, Bressolle F, et al.
  Inter- and intra-individual variation in
  transdermal fentanyl absorption in cancer pain
  patients. Oncology Reports 141029-1036, 2005.

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Absorption Kinetics
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Absorption Kinetics
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Absorption Kinetics
175 mcg/hr
100 mcg/hr
125 mcg/hr
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Results

• Significant findings (P lt 0.05)
• Age lt65, 65-75, gt75
• 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 lt38, 38-40, gt40
• P 0.051

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Limitations

• Indirect assay

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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.

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Absorption Kinetics
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Absorption Kinetics
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Clinical Pearls

• Avoid cutting patches.
• Avoid occlusive bandages.
• Avoid heat.
• Dose according to patient response.
• Sustained release after removal.

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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 612289-2307, 2001.
• Solassol I, Caumette L, Bressolle F, et al.
  Inter- and intra-individual variation in
  transdermal fentanyl absorption in cancer pain
  patients. Oncology Reports 141029-1036, 2005.