absorptive kinetics of transdermal fentanyl robert leonard, pharmd candidate university of florida...
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Absorptive Kinetics of Transdermal Fentanyl
Robert Leonard, PharmD candidateUniversity of FloridaCollege of Pharmacy
Overview
Rationale Barriers TTS-fentanyl Pharmacokinetics Studies of pharmacokinetic variability
Rationale
Continuous infusion Noninvasive nature Special populations
– Protracted vomiting– Dysphagia
Less frequent dosing
Barriers
Epidermal microflora Stratum corneum Subcutaneous vasculature Physicochemical properties
– MW– Lipophilicity
TTS-fentanyl
Pharmacokinetics
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
Kinetics
Kinetics
Elimination– Cl = 34.2 – 52.8L/hr– T1/2 = 17hrs (after removal)
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 Kinetics
Absorption Kinetics
Absorption Kinetics
175 mcg/hr100 mcg/hr 125 mcg/hr
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
Indirect assay
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.
Absorption Kinetics
Absorption Kinetics
Clinical Pearls
Avoid cutting patches. Avoid occlusive bandages. Avoid heat. Dose according to patient response. Sustained release after removal.
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.