Abstract
PurposeTransdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route.MethodsFifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model.ResultsA one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h−1, respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed.ConclusionsWe describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-015-2005-x) contains supplementary material, which is available to authorized users.
Highlights
For the treatment of moderate to severe cancer-related pain, strong opioids are the treatment of choice [1, 2]
We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice
Male Female Race Caucasian Other Unknown WHO performance status 0 1 2 3 Unknown Median body mass index—range Median NRS in rest at start of fentanyl or on admission—range Primary tumour localization Breast Colorectal Prostate Soft tissue sarcoma/GIST Urinary tract Other Median albumin—range Median AST (U/l)—range Median ALT (U/l)—range Median total bilirubin—range treatment with td fentanyl without previous or concurrent sc treatment; and in 32 patients, samples were available during treatment with sc or td fentanyl, but the other treatment route was given until shortly before sampling or simultaneously
Summary
We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route
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