Individualisation of leflunomide dosing in rheumatoid arthritis patients /

dc.contributor.authorHopkins, Ashley Mark,
dc.contributor.schoolUniversity of South Australia. School of Pharmacy and Medical Sciences.
dc.contributor.schoolSchool of Pharmacy and Medical Sciences.
dc.date.issued2016
dc.description1 ethesis (xxiv, 275 pages) :
dc.descriptionillustrations (some colour)
dc.descriptionIncludes bibliographical references (pages 155-171)
dc.description.abstractHistorically, leflunomide has been a second-line disease modifying anti-rheumatic drug (DMARD), initiated in those who fail to respond to methotrexate-based therapies. Nowadays, those who fail to respond to leflunomide tend to progress to expensive biological agents. Leflunomide’s therapeutic effects occur through the inhibition of the mitochondrial enzyme dihydro-oroate dehydrogenase within T-lymphocytes by its active metabolite, teriflunomide. Given teriflunomide has highly variable pharmacokinetics between individuals (that may be influenced by pharmacogenetic variants), relatively consistent within individual pharmacokinetic variability and there is a documented concentration-response relationship, leflunomide appears to be an ideal candidate for personalised dosing strategies. The aim of this thesis was to review leflunomide’s place in therapy and assist the development of individualisation strategies for leflunomide dosing in rheumatoid arthritis (RA) patients, thereby minimising the wide variability in response and toxicity to therapy. To achieve this, qualitative and pharmacoepidemiological studies were conducted to investigate treatment strategies employed by Australian rheumatologists, while novel variants and pharmacometric modelling techniques were explored to assist the development of individualisation strategies for leflunomide.
dc.description.dissertationThesis (PhD)--University of South Australia, 2016.
dc.identifier.urihttps://hdl.handle.net/11541.2/122693
dc.language.isoen
dc.provenanceCopyright 2015 Ashley Hopkins
dc.subject.lcshLeflunomide
dc.subject.lcshRheumatoid arthritis
dc.titleIndividualisation of leflunomide dosing in rheumatoid arthritis patients /
dc.typethesis
dcterms.accessRights506 0#$fstar $2Unrestricted online access
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