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dc.contributor.authorNath, Christa Ellen-
dc.contributor.authorGrigg, Andrew P-
dc.contributor.authorRosser, Sebastian P A-
dc.contributor.authorEstell, Jane-
dc.contributor.authorNewman, Elizabeth-
dc.contributor.authorTiley, Campbell-
dc.contributor.authorRamanathan, Sundra-
dc.contributor.authorHo, Shir Jing-
dc.contributor.authorLarsen, Stephen-
dc.contributor.authorGibson, John-
dc.contributor.authorPresgrave, Peter-
dc.contributor.authorShaw, Peter John-
dc.contributor.authorTrotman, Judith-
dc.identifier.citationEuropean Journal of Clinical Pharmacology 2022en
dc.description.abstractTo evaluate the accuracy of melphalan test dose pharmacokinetic (PK) predictions of the subsequent high dose (HDM) area under the concentration-versus-time curve (AUC) and to identify sources of prediction error (PE). A prospective multicentre PK study was conducted in 40 myeloma patients of median age 60 (range:35-71) years using a 20 mg/m2 test dose administered 1-3 days prior to HDM (predominantly 180 mg/m2). PK data were collected post the test and high doses to compare predicted versus actual AUCs determined using the trapezoidal rule. Test and high dose infusion concentration, volume and duration and the time from preparation to infusion were compared using the paired Wilcoxin rank sign test. The impact of Melphalan administration parameters on PE was evaluated using the Mann-Whitney test. The predictive capacity of a previously published population PK (PopPK) model was also examined. Predicted HDM AUC was within 15% of the observed values in only 63% of patients when analysed using the trapezoidal rule and 70% of patients using PopPK. Test dose infusion concentration, volume, duration and time from preparation to infusion were significantly lower than for HDM (p < 0.005). Test dose administration within 15 min of reconstitution (n = 5) was associated with significantly lower PE than administration times of 16-60 min (n = 22), p < 0.05. Test and HDM infusion concentrations were lower in patients with large PE (> ± 15%), but the differences were not significant (p = 0.078, 0.228, respectively). Test dose PK has the potential to predict subsequent HDM exposure to achieve a target AUC once melphalan administration parameters are optimised to account for stability issues in the formulation.en
dc.subjectPharmacokinetic predictionsen
dc.subjectTest doseen
dc.titleChallenges associated with test dose pharmacokinetic predictions of high dose melphalan exposure in patients with multiple myeloma.en
dc.typeJournal Articleen
dc.identifier.journaltitleEuropean Journal of Clinical Pharmacologyen
dc.identifier.affiliationHaematology Department, Wollongong Hospital, Wollongong, Australiaen
dc.identifier.affiliationHaematology Department, Gosford Hospital, Gosford, Australiaen
dc.identifier.affiliationClinical Haematologyen
dc.identifier.affiliationHaematology Department, St George Hospital, Kogarah, Australiaen
dc.identifier.affiliationThe University of New South Wales, Kensington, Australiaen
dc.identifier.affiliationHaematology Department, Royal Prince Alfred Hospital, Camperdown, Australiaen
dc.identifier.affiliationBiochemistry Department, The Children's Hospital at Westmead, Westmead, Australiaen
dc.identifier.affiliationCancer Centre for Children, The Children's Hospital at Westmead, Westmead, Australiaen
dc.identifier.affiliationHaematology Department, Concord Repatriation General Hospital, Concord, Australiaen
dc.identifier.affiliationFaculty of Health and Medicine, The University of Sydney, Camperdown, Australiaen
dc.identifier.pubmedid36205743-, Andrew P
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
item.grantfulltextnone- Newton-John Cancer Wellness and Research Centre- Haematology-
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