title: Exposure to Fentanyl After Transdermal Patch Administration for Cancer Pain Management.
abstract: This study aimed to describe exposure after fentanyl transdermal patch administration in patients with advanced cancer to quantify variability around the exposure. Patients (n  =  56) with advanced cancer who received transdermal fentanyl (Durogesic®; median dose, 50 μg/h; range, 12-200 μg/h) provided venous blood samples (n  =  163) at various times (0.5-72 hours) during several patch application intervals. Plasma fentanyl concentration was determined (median, 0.9 μg/L; range, 0.04-9.7 μg/L) by high-performance liquid chromatography coupled to tandem mass spectrometry. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling with NONMEM. A 1-compartment distribution model with first-order absorption and elimination described fentanyl exposure after transdermal patch administration. Fentanyl apparent clearance (between-subject variability [BSV], %) was estimated at 122 L/h/70 kg and 38.5%, respectively. The absorption rate constant was 0.013 h(-1) . Between-occasion variability on apparent clearance was 22.0%, which was lower than BSV, suggesting predictable exposure within the same patient and justifying therapeutic drug monitoring. Except for weight-based dosing, no other patient characteristic could be identified to guide initial fentanyl dose selection in patients with advanced cancer.
authors.affiliation: School of Pharmacy, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.|Mater Research Institute-The University of Queensland, Brisbane, Australia.
authors.forename: Sudeep R
authors.initials: SR
authors.lastname: Bista
authors.affiliation: School of Pharmacy, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.|Mater Research Institute-The University of Queensland, Brisbane, Australia.
authors.forename: Alison
authors.initials: A
authors.lastname: Haywood
authors.affiliation: Mater Research Institute-The University of Queensland, Brisbane, Australia.|Department of Palliative and Supportive Care, Mater Health Services, Brisbane, Australia.
authors.forename: Janet
authors.initials: J
authors.lastname: Hardy
authors.affiliation: School of Pharmacy, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.|Mater Research Institute-The University of Queensland, Brisbane, Australia.|St Vincent's Clinical School, University of New South Wales, New South Wales, Australia.|SydPath, St Vincent's Hospital, Sydney, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Norris
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, Australia.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hennig
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood; D000072716:Cancer Pain / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D059408:Pain Management / Q000379:methods*; D062606:Tertiary Care Centers; D057968:Transdermal Patch
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl
keywords: cancer pain; fentanyl; plasma; population pharmacokinetics; transdermal patch