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Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients
Erasmus MC Canc Inst, Dept Med Oncol, Groene Hilledijk 301, NL-3075 EA Rotterdam, Netherlands..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Univ Coimbra, Fac Pharm, Dept Pharmacol, Coimbra, Portugal.;Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Coimbra, Portugal..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Erasmus MC Canc Inst, Dept Med Oncol, Groene Hilledijk 301, NL-3075 EA Rotterdam, Netherlands..
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2016 (English)In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 72, no 4, 459-467 p.Article in journal (Refereed) Published
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Abstract [en]

Transdermal 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. Fifty-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. A 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. 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.

Place, publisher, year, edition, pages
2016. Vol. 72, no 4, 459-467 p.
Keyword [en]
Fentanyl, Pharmacokinetics, Subcutaneous, Transdermal, NONMEM
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-283756DOI: 10.1007/s00228-015-2005-xISI: 000372172200008PubMedID: 26762381OAI: oai:DiVA.org:uu-283756DiVA: diva2:919703
Available from: 2016-04-14 Created: 2016-04-14 Last updated: 2017-11-30Bibliographically approved

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Abrantes, João A.Jönsson, Siv

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