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.