Exposure to Fentanyl After Transdermal Patch Administration for Cancer Pain Management

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(R); median dose, 50 mu g/h; range, 12-200 mu g/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 mu g/L; range, 0.04-9.7 mu g/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.