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Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients
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| Veröffentlicht in: | Scientific reports 9(2019) Artikel-Nummer 14635, 6 Seiten |
|---|---|
| Personen und Körperschaften: | , , , , , |
| Titel: | Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients/ Marcus J.P. Geist, Victoria C. Ziesenitz, Hubert J. Bardenheuer, Juergen Burhenne, Gisela Skopp & Gerd Mikus |
| Format: | E-Book-Kapitel |
| Sprache: | Englisch |
| veröffentlicht: |
10 October 2019
|
| Gesamtaufnahme: |
: Scientific reports, 9(2019) Artikel-Nummer 14635, 6 Seiten
, volume:9 |
| Quelle: | Verbunddaten SWB Lizenzfreie Online-Ressourcen |
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| 520 | |a Transdermal fentanyl is widely used to control pain in cancer patients. The high pharmacokinetic variability of fentanyl is assumed to be due to cytochrome P450 3A-mediated (CYP3A) N-dealkylation to norfentanyl in humans. However, recently published clinical studies question the importance of the described metabolic pathway. In this small study in palliative cancer patients under real-life clinical conditions, the influence of CYP3A on fentanyl variability was investigated. In addition to the determination of midazolam plasma concentration to reveal CYP3A activity, plasma concentrations of fentanyl and its metabolite, norfentanyl, were measured in identical blood samples of 20 patients who participated in an ongoing trial and had been on transdermal fentanyl. Fentanyl, norfentanyl, midazolam, and 1′-OH-midazolam were quantified by liquid chromatography/tandem mass spectrometry. Plasma concentrations of fentanyl and norfentanyl exhibited a large variability. Mean estimated total clearance of fentanyl and mean metabolic clearance of midazolam (as a marker of CYP3A activity) were 75.5 and 36.3 L/h. Both clearances showed a weak correlation and hence a minimal influence of CYP3A on fentanyl elimination. | ||
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| author | Geist, Marcus Julian Peter, Ziesenitz, Victoria C., Bardenheuer, Hubert J., Burhenne, Jürgen, Skopp, Gisela, Mikus, Gerd |
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| contents | Transdermal fentanyl is widely used to control pain in cancer patients. The high pharmacokinetic variability of fentanyl is assumed to be due to cytochrome P450 3A-mediated (CYP3A) N-dealkylation to norfentanyl in humans. However, recently published clinical studies question the importance of the described metabolic pathway. In this small study in palliative cancer patients under real-life clinical conditions, the influence of CYP3A on fentanyl variability was investigated. In addition to the determination of midazolam plasma concentration to reveal CYP3A activity, plasma concentrations of fentanyl and its metabolite, norfentanyl, were measured in identical blood samples of 20 patients who participated in an ongoing trial and had been on transdermal fentanyl. Fentanyl, norfentanyl, midazolam, and 1′-OH-midazolam were quantified by liquid chromatography/tandem mass spectrometry. Plasma concentrations of fentanyl and norfentanyl exhibited a large variability. Mean estimated total clearance of fentanyl and mean metabolic clearance of midazolam (as a marker of CYP3A activity) were 75.5 and 36.3 L/h. Both clearances showed a weak correlation and hence a minimal influence of CYP3A on fentanyl elimination. |
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| spelling | Geist, Marcus Julian Peter 1981- VerfasserIn (DE-588)136086713 (DE-627)57715009X (DE-576)300822995 aut, Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients Marcus J.P. Geist, Victoria C. Ziesenitz, Hubert J. Bardenheuer, Juergen Burhenne, Gisela Skopp & Gerd Mikus, 10 October 2019, 6, Text txt rdacontent, Computermedien c rdamedia, Online-Ressource cr rdacarrier, Gesehen am 10.12.2019, Transdermal fentanyl is widely used to control pain in cancer patients. The high pharmacokinetic variability of fentanyl is assumed to be due to cytochrome P450 3A-mediated (CYP3A) N-dealkylation to norfentanyl in humans. However, recently published clinical studies question the importance of the described metabolic pathway. In this small study in palliative cancer patients under real-life clinical conditions, the influence of CYP3A on fentanyl variability was investigated. In addition to the determination of midazolam plasma concentration to reveal CYP3A activity, plasma concentrations of fentanyl and its metabolite, norfentanyl, were measured in identical blood samples of 20 patients who participated in an ongoing trial and had been on transdermal fentanyl. Fentanyl, norfentanyl, midazolam, and 1′-OH-midazolam were quantified by liquid chromatography/tandem mass spectrometry. Plasma concentrations of fentanyl and norfentanyl exhibited a large variability. Mean estimated total clearance of fentanyl and mean metabolic clearance of midazolam (as a marker of CYP3A activity) were 75.5 and 36.3 L/h. Both clearances showed a weak correlation and hence a minimal influence of CYP3A on fentanyl elimination., Ziesenitz, Victoria C. 1985- VerfasserIn (DE-588)1036795640 (DE-627)751696099 (DE-576)386865132 aut, Bardenheuer, Hubert J. VerfasserIn (DE-588)1064859208 (DE-627)815238819 (DE-576)424204681 aut, Burhenne, Jürgen 1963- VerfasserIn (DE-588)1034228889 (DE-627)745126987 (DE-576)381858197 aut, Skopp, Gisela 1951- VerfasserIn (DE-588)1060738538 (DE-627)800969413 (DE-576)164452346 aut, Mikus, Gerd VerfasserIn (DE-588)110903137 (DE-627)691097941 (DE-576)336988710 aut, Enthalten in Scientific reports [London] : Macmillan Publishers Limited, part of Springer Nature, 2011 9(2019) Artikel-Nummer 14635, 6 Seiten Online-Ressource (DE-627)663366712 (DE-600)2615211-3 (DE-576)346641179 2045-2322 nnns, volume:9 year:2019 extent:6, https://doi.org/10.1038/s41598-019-51279-6 Verlag Resolving-System kostenfrei Volltext, https://www.nature.com/articles/s41598-019-51279-6 Verlag kostenfrei Volltext, https://doi.org/10.1038/s41598-019-51279-6 LFER, https://www.nature.com/articles/s41598-019-51279-6 LFER, LFER 2019-12-18T00:00:00Z |
| spellingShingle | Geist, Marcus Julian Peter, Ziesenitz, Victoria C., Bardenheuer, Hubert J., Burhenne, Jürgen, Skopp, Gisela, Mikus, Gerd, Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients, Transdermal fentanyl is widely used to control pain in cancer patients. The high pharmacokinetic variability of fentanyl is assumed to be due to cytochrome P450 3A-mediated (CYP3A) N-dealkylation to norfentanyl in humans. However, recently published clinical studies question the importance of the described metabolic pathway. In this small study in palliative cancer patients under real-life clinical conditions, the influence of CYP3A on fentanyl variability was investigated. In addition to the determination of midazolam plasma concentration to reveal CYP3A activity, plasma concentrations of fentanyl and its metabolite, norfentanyl, were measured in identical blood samples of 20 patients who participated in an ongoing trial and had been on transdermal fentanyl. Fentanyl, norfentanyl, midazolam, and 1′-OH-midazolam were quantified by liquid chromatography/tandem mass spectrometry. Plasma concentrations of fentanyl and norfentanyl exhibited a large variability. Mean estimated total clearance of fentanyl and mean metabolic clearance of midazolam (as a marker of CYP3A activity) were 75.5 and 36.3 L/h. Both clearances showed a weak correlation and hence a minimal influence of CYP3A on fentanyl elimination. |
| title | Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients |
| title_auth | Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients |
| title_full | Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients Marcus J.P. Geist, Victoria C. Ziesenitz, Hubert J. Bardenheuer, Juergen Burhenne, Gisela Skopp & Gerd Mikus |
| title_fullStr | Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients Marcus J.P. Geist, Victoria C. Ziesenitz, Hubert J. Bardenheuer, Juergen Burhenne, Gisela Skopp & Gerd Mikus |
| title_full_unstemmed | Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients Marcus J.P. Geist, Victoria C. Ziesenitz, Hubert J. Bardenheuer, Juergen Burhenne, Gisela Skopp & Gerd Mikus |
| title_in_hierarchy | Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients / Marcus J.P. Geist, Victoria C. Ziesenitz, Hubert J. Bardenheuer, Juergen Burhenne, Gisela Skopp & Gerd Mikus, |
| title_short | Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients |
| title_sort | minor contribution of cytochrome p450 3a activity on fentanyl exposure in palliative care cancer patients |
| url | https://doi.org/10.1038/s41598-019-51279-6, https://www.nature.com/articles/s41598-019-51279-6 |