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Absorptive Kinetics of Transdermal Fentanyl
Robert Leonard, PharmD candidateUniversity of FloridaCollege 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 14:1029-1036, 2005.
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Absorption Kinetics
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Absorption Kinetics
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Absorption Kinetics
175 mcg/hr100 mcg/hr 125 mcg/hr
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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
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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 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.