Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants
Aim Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 μg/mL for procedural pain. Methods Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3–34.1 weeks) and 2 μ...
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| Veröffentlicht in: | Acta Paediatrica 2019-08, Vol.108 (8), p.1441-1446 |
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| container_title | Acta Paediatrica |
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| creator | Norman, Elisabeth Kindblom, Jenny M. Rane, Anders Berg, Ann‐Cathrine Schubert, Ulf Hallberg, Boubou Fellman, Vineta |
| description | Aim
Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 μg/mL for procedural pain.
Methods
Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3–34.1 weeks) and 2 μg/kg (n = 8, 27.4; 25.3–30.7 weeks) fentanyl, respectively, before skin‐breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed.
Results
The median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/mL at 15–31 minutes, two and four hours and the half‐lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low‐ and high‐dose groups, respectively. A significant correlation was seen between weight at study inclusion and half‐life (Spearman′s r = −0.9, p |
| doi_str_mv | 10.1111/apa.14744 |
| format | Article |
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Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 μg/mL for procedural pain.
Methods
Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3–34.1 weeks) and 2 μg/kg (n = 8, 27.4; 25.3–30.7 weeks) fentanyl, respectively, before skin‐breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed.
Results
The median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/mL at 15–31 minutes, two and four hours and the half‐lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low‐ and high‐dose groups, respectively. A significant correlation was seen between weight at study inclusion and half‐life (Spearman′s r = −0.9, p < 0.001), volume of distribution (r = −0.8, p < 0.01) and clearance (r = −0.9, p < 0.01) in the low‐dose group (n = 9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated.
Conclusion
The inter‐individual variation of fentanyl pharmacokinetics is large in preterm infants, and the dose of 0.5 μg/kg seems not effective for skin‐breaking procedures.</description><identifier>ISSN: 0803-5253</identifier><identifier>EISSN: 1651-2227</identifier><identifier>DOI: 10.1111/apa.14744</identifier><identifier>PMID: 30721546</identifier><language>eng</language><publisher>Norway: Wiley Subscription Services, Inc</publisher><subject>analgesia ; Basic Medicine ; Clinical Medicine ; continuous-infusion ; Fentanyl ; Gestational age ; Infants ; initial validation ; Intubation ; Klinisk medicin ; management ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Medicinska och farmaceutiska grundvetenskaper ; morphine ; Newborn babies ; newborns ; outcomes ; Pain ; Pediatrics ; Pediatrik ; Pharmacodynamics ; Pharmacokinetics ; Premature babies ; Preterm infants ; procedural pain ; Samhällsfarmaci och klinisk farmaci ; scale ; Skin ; Social and Clinical Pharmacy</subject><ispartof>Acta Paediatrica, 2019-08, Vol.108 (8), p.1441-1446</ispartof><rights>2019 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd</rights><rights>2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5244-e142573e70c31dbb088af01e3c29bbb9e2b5e352e39be172a260a09580d7ef23</citedby><cites>FETCH-LOGICAL-c5244-e142573e70c31dbb088af01e3c29bbb9e2b5e352e39be172a260a09580d7ef23</cites><orcidid>0000-0002-1355-5633 ; 0000-0002-5495-7508 ; 0000-0001-6346-8899 ; 0000-0003-0028-2143</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fapa.14744$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fapa.14744$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30721546$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://gup.ub.gu.se/publication/282257$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://lup.lub.lu.se/record/c5254b41-d71f-4281-88fe-02c7ea4e459a$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:141353541$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Norman, Elisabeth</creatorcontrib><creatorcontrib>Kindblom, Jenny M.</creatorcontrib><creatorcontrib>Rane, Anders</creatorcontrib><creatorcontrib>Berg, Ann‐Cathrine</creatorcontrib><creatorcontrib>Schubert, Ulf</creatorcontrib><creatorcontrib>Hallberg, Boubou</creatorcontrib><creatorcontrib>Fellman, Vineta</creatorcontrib><title>Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants</title><title>Acta Paediatrica</title><addtitle>Acta Paediatr</addtitle><description>Aim
Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 μg/mL for procedural pain.
Methods
Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3–34.1 weeks) and 2 μg/kg (n = 8, 27.4; 25.3–30.7 weeks) fentanyl, respectively, before skin‐breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed.
Results
The median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/mL at 15–31 minutes, two and four hours and the half‐lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low‐ and high‐dose groups, respectively. A significant correlation was seen between weight at study inclusion and half‐life (Spearman′s r = −0.9, p < 0.001), volume of distribution (r = −0.8, p < 0.01) and clearance (r = −0.9, p < 0.01) in the low‐dose group (n = 9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated.
Conclusion
The inter‐individual variation of fentanyl pharmacokinetics is large in preterm infants, and the dose of 0.5 μg/kg seems not effective for skin‐breaking procedures.</description><subject>analgesia</subject><subject>Basic Medicine</subject><subject>Clinical Medicine</subject><subject>continuous-infusion</subject><subject>Fentanyl</subject><subject>Gestational age</subject><subject>Infants</subject><subject>initial validation</subject><subject>Intubation</subject><subject>Klinisk medicin</subject><subject>management</subject><subject>Medical and Health Sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicinska och farmaceutiska grundvetenskaper</subject><subject>morphine</subject><subject>Newborn babies</subject><subject>newborns</subject><subject>outcomes</subject><subject>Pain</subject><subject>Pediatrics</subject><subject>Pediatrik</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>Premature babies</subject><subject>Preterm infants</subject><subject>procedural pain</subject><subject>Samhällsfarmaci och klinisk farmaci</subject><subject>scale</subject><subject>Skin</subject><subject>Social and Clinical Pharmacy</subject><issn>0803-5253</issn><issn>1651-2227</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kU1v1DAQhi0EosvCgT-AInHikNafm-S4qgpUWgkOPXGxxsmkuE2cYCet9t8z22z31loaefT6mXdsD2OfBT8XtC5ghHOhC63fsJXYGJFLKYu3bMVLrnIjjTpjH1K641yqSm_eszPFCymM3qzYn-vQ-AffzNBlDxA9TH4IKfMhazFMEPZdNv6F2EM93PuAk69TBqE5ic0-QH8QqWKMOGHsKW0hTOkje9dCl_DTcV-zm-9XN5c_892vH9eX211eG6l1jkJLUygseK1E4xwvS2i5QFXLyjlXoXQGlZGoKoeikCA3HHhlSt4U2Eq1Zvlimx5xnJ0do-8h7u0A3h6le8rQ6pK-RRC_e5Hv5pHCURwK6H5GOy1sU4jWalkKW5YtWi7rAkGjNhW82v6W7Ei6fXKT1J7euWZfF36Mw78Z02TvhjkG-iBL59SEb6Qm6ttC1XFIKWJ78hXcHmZuaeb2aebEfjk6zq7H5kQ-D5mAiwV49B3uX3ay29_bxfI_fNy3Hw</recordid><startdate>201908</startdate><enddate>201908</enddate><creator>Norman, Elisabeth</creator><creator>Kindblom, Jenny M.</creator><creator>Rane, Anders</creator><creator>Berg, Ann‐Cathrine</creator><creator>Schubert, Ulf</creator><creator>Hallberg, Boubou</creator><creator>Fellman, Vineta</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TS</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>F1U</scope><scope>D95</scope><orcidid>https://orcid.org/0000-0002-1355-5633</orcidid><orcidid>https://orcid.org/0000-0002-5495-7508</orcidid><orcidid>https://orcid.org/0000-0001-6346-8899</orcidid><orcidid>https://orcid.org/0000-0003-0028-2143</orcidid></search><sort><creationdate>201908</creationdate><title>Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants</title><author>Norman, Elisabeth ; Kindblom, Jenny M. ; Rane, Anders ; Berg, Ann‐Cathrine ; Schubert, Ulf ; Hallberg, Boubou ; Fellman, Vineta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5244-e142573e70c31dbb088af01e3c29bbb9e2b5e352e39be172a260a09580d7ef23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>analgesia</topic><topic>Basic Medicine</topic><topic>Clinical Medicine</topic><topic>continuous-infusion</topic><topic>Fentanyl</topic><topic>Gestational age</topic><topic>Infants</topic><topic>initial validation</topic><topic>Intubation</topic><topic>Klinisk medicin</topic><topic>management</topic><topic>Medical and Health Sciences</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicinska och farmaceutiska grundvetenskaper</topic><topic>morphine</topic><topic>Newborn babies</topic><topic>newborns</topic><topic>outcomes</topic><topic>Pain</topic><topic>Pediatrics</topic><topic>Pediatrik</topic><topic>Pharmacodynamics</topic><topic>Pharmacokinetics</topic><topic>Premature babies</topic><topic>Preterm infants</topic><topic>procedural pain</topic><topic>Samhällsfarmaci och klinisk farmaci</topic><topic>scale</topic><topic>Skin</topic><topic>Social and Clinical Pharmacy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Norman, Elisabeth</creatorcontrib><creatorcontrib>Kindblom, Jenny M.</creatorcontrib><creatorcontrib>Rane, Anders</creatorcontrib><creatorcontrib>Berg, Ann‐Cathrine</creatorcontrib><creatorcontrib>Schubert, Ulf</creatorcontrib><creatorcontrib>Hallberg, Boubou</creatorcontrib><creatorcontrib>Fellman, Vineta</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Physical Education Index</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Göteborgs universitet</collection><collection>SWEPUB Lunds universitet</collection><jtitle>Acta Paediatrica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Norman, Elisabeth</au><au>Kindblom, Jenny M.</au><au>Rane, Anders</au><au>Berg, Ann‐Cathrine</au><au>Schubert, Ulf</au><au>Hallberg, Boubou</au><au>Fellman, Vineta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants</atitle><jtitle>Acta Paediatrica</jtitle><addtitle>Acta Paediatr</addtitle><date>2019-08</date><risdate>2019</risdate><volume>108</volume><issue>8</issue><spage>1441</spage><epage>1446</epage><pages>1441-1446</pages><issn>0803-5253</issn><eissn>1651-2227</eissn><abstract>Aim
Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 μg/mL for procedural pain.
Methods
Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3–34.1 weeks) and 2 μg/kg (n = 8, 27.4; 25.3–30.7 weeks) fentanyl, respectively, before skin‐breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed.
Results
The median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/mL at 15–31 minutes, two and four hours and the half‐lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low‐ and high‐dose groups, respectively. A significant correlation was seen between weight at study inclusion and half‐life (Spearman′s r = −0.9, p < 0.001), volume of distribution (r = −0.8, p < 0.01) and clearance (r = −0.9, p < 0.01) in the low‐dose group (n = 9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated.
Conclusion
The inter‐individual variation of fentanyl pharmacokinetics is large in preterm infants, and the dose of 0.5 μg/kg seems not effective for skin‐breaking procedures.</abstract><cop>Norway</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30721546</pmid><doi>10.1111/apa.14744</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-1355-5633</orcidid><orcidid>https://orcid.org/0000-0002-5495-7508</orcidid><orcidid>https://orcid.org/0000-0001-6346-8899</orcidid><orcidid>https://orcid.org/0000-0003-0028-2143</orcidid></addata></record> |
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| ispartof | Acta Paediatrica, 2019-08, Vol.108 (8), p.1441-1446 |
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| language | eng |
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| source | Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | analgesia Basic Medicine Clinical Medicine continuous-infusion Fentanyl Gestational age Infants initial validation Intubation Klinisk medicin management Medical and Health Sciences Medicin och hälsovetenskap Medicinska och farmaceutiska grundvetenskaper morphine Newborn babies newborns outcomes Pain Pediatrics Pediatrik Pharmacodynamics Pharmacokinetics Premature babies Preterm infants procedural pain Samhällsfarmaci och klinisk farmaci scale Skin Social and Clinical Pharmacy |
| title | Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants |
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