Absorptive Kinetics of Transdermal Fentanyl Robert Leonard Pharm

Absorptive Kinetics of Transdermal Fentanyl Robert Leonard, Pharm. D candidate University of Florida College of Pharmacy

Overview l l l Rationale Barriers TTS-fentanyl Pharmacokinetics Studies of pharmacokinetic variability

Rationale l l l Continuous infusion Noninvasive nature Special populations – – l Protracted vomiting Dysphagia Less frequent dosing

Barriers l l Epidermal microflora Stratum corneum Subcutaneous vasculature Physicochemical properties – – MW Lipophilicity

TTS-fentanyl

Pharmacokinetics

Kinetics l Absorption – – – l Distribution – l F = 0. 92 Protein binding = 79 - 97% Tmax = 35 hours Vd = 3 – 8 L/kg Metabolism – – – CYP 3 A 4 Major: norfentanyl Minor: hydroxyfentanyl, hydroxynorfentanyl, despropionylfentanyl

Kinetics

Kinetics l Elimination – – Cl = 34. 2 – 52. 8 L/hr T 1/2 = 17 hrs (after removal)

Study l Solassol I, Caumette L, Bressolle F, et al. “Inter- and intra-individual variation in transdermal fentanyl absorption in cancer pain patients. ” Oncology Reports 14: 10291036, 2005.

Absorption Kinetics

Absorption Kinetics

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

Results l Significant findings (P < 0. 05) – Age: <65, 65 -75, >75 l – Primary cancer location: head and neck, GI, GU, Lung, Brest, others l l P = 0. 030 P = 0. 006 Findings approaching significance (P ≤ 0. 06) – Occlusive bandage: yes, no l – P = 0. 060 Temperature: <38, 38 -40, >40 l P = 0. 051

Limitations l Indirect assay

Study l 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 l l l 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 intraindividual variation in transdermal fentanyl absorption in cancer pain patients. ” Oncology Reports 14: 1029 -1036, 2005.