Paracetamol metabolism in postoperative patients

Simple item page
dc.contributor.advisorKennedy, Julia M.
dc.contributor.advisorByrne, Stephen
dc.contributor.advisorCreaton, Geraldine
dc.contributor.authorMurphy, Philip Gerard MacHale
dc.date.accessioned2012-05-02T13:09:35Z
dc.date.available2012-05-02T13:09:35Z
dc.date.issued2012-01
dc.date.submitted2012-01-19
dc.description.abstractIntroduction: Despite being available for more than 50 years, there is still much to learn about paracetamol. Postoperative analgesic regimens that maintain good pain control while minimising exposure to opiates are beneficial and paracetamol has had a resurgence in this role since an IV formulation came to market. However there is evidence to suggest currently licensed doses are sub-therapeutic, especially when administered orally or rectally. Higher, unlicensed doses are now being advocated but, prior to this study, there was little evidence of their safety in surgical patients. When assessing drug safety in surgical patients a number of surgery and patient related factors influence results, and these must be considered. Methods: Major and intermediate surgical patients were recruited from two hospitals in Ireland. They were administered IV paracetamol at either 9g or 4g daily doses. In addition they received daily sub therapeutic doses of four other medicines to indicate the activity of their CYP450 enzymes that are involved in paracetamol metabolism. Urine and blood samples were collected to determine paracetamol pharmacokinetics, CYP450 activity, inflammatory cytokine concentration and for evidence of hepatotoxicity. Results: There were 33 patients that participated in the study. There was no evidence of clinically significant hepatotoxicity occurring in any patient during the study period, but there could have been changes following this time. Paracetamol disposition was shown to change, however half-life remained relatively constant. There were a number of changes to the way paracetamol was metabolised following surgery that maintained this rate of elimination. Conclusion: Doses of up to 9g per day given to major surgical patients for up to five days postoperatively produced no evidence of hepatotoxicity. Further research is warranted to determine the clinical utility of these higher dosesen
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMurphy, P.G., 2012. Paracetamol metabolism in postoperative patients. PhD Thesis, University College Cork.en
dc.identifier.urihttps://hdl.handle.net/10468/573
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2012, Philip Gerard MacHale Murphyen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectParacetamolen
dc.subjectHPLCen
dc.subjectClinical studyen
dc.subject.lcshAcetaminophenen
dc.subject.lcshDrugs--Metabolismen
dc.subject.lcshPharmacokineticsen
dc.subject.lcshHigh performance liquid chromatographyen
dc.subject.lcshDrugs--Testingen
dc.titleParacetamol metabolism in postoperative patientsen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Medicine & Health)en
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
MurphyPG_PhD2012.pdf
Size:
11.7 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 2 of 2
Thumbnail Image
Name:
license.txt
Size:
5.75 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Thumbnail Image
Name:
573Licence.pdf
Size:
121.27 KB
Format:
Adobe Portable Document Format
Description:
License
Collections
Doctoral Theses
College of Medicine and Health - Doctoral Theses
Pharmacy - Doctoral Theses