Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorNath, C.E.en
dc.contributor.authorShaw, P.J.en
dc.contributor.authorTrotman, J.en
dc.contributor.authorZeng, L.en
dc.contributor.authorDuffull, S.en
dc.contributor.authorHegarty, G.en
dc.contributor.authorMcLachlan, Andrewen
dc.contributor.authorGurney, H.en
dc.contributor.authorKerridge, Ianen
dc.contributor.authorKwan, Yiu Lamen
dc.contributor.authorPresgrave, P.en
dc.contributor.authorTiley, Campbellen
dc.contributor.authorJoshua, D.en
dc.contributor.authorEarl, J.W.en
dc.identifier.citationVolume 69, Issue 5, pp. 484-497en
dc.description.abstractAIMS: To i) investigate the pharmacokinetics of total and unbound plasma melphalan using a population approach, ii) identify clinical factors that affect melphalan disposition and iii) evaluate the role of melphalan exposure in melphalan-related toxicity and disease response. METHODS: Population pharmacokinetic modelling (using NONMEM) was performed with total and unbound concentration-time data from 100 patients (36-73 years) who had received a median 192 mg m(-2) melphalan dose. Model derived estimates of total and unbound melphalan exposure (AUC) in patients with serious melphalan toxicity and those who had a good disease response (>or=90% decrease in paraprotein concentrations) were compared using the Mann-Whitney test. RESULTS: A two compartment model generated population mean estimates for total and unbound melphalan clearance (CL) of 27.8 and 128 l h(-1), respectively. Estimated creatinine clearance, fat free mass and haematocrit were important determinants of total and unbound CL, reducing the inter-individual variability in total CL from 34% to 27% and in unbound CL from 42% to 30%. Total AUC (range 4.9-24.4 mg l(-1) h) and unbound AUC (range 1.0-6.5 mg l(-1) h) were significantly higher in patients who had oral mucositis (>or=grade 3) and long hospital admissions (P < 0.01). Patients who responded well had significantly higher unbound AUC (median 3.2 vs. 2.8 mg l(-1) h, P < 0.05) when assessed from diagnosis to post-melphalan and higher total AUC (median 21.3 vs. 13.4 mg l(-1) h, P= 0.06), when assessed from pre- to post-melphalan. CONCLUSIONS: Creatinine clearance, fat free mass and haematocrit influence total and unbound melphalan plasma clearance. Melphalan exposure is related to melphalan toxicity while the association with efficacy shows promising trends that will be studied further.en
dc.subjectDrug Therapyen
dc.titlePopulation Pharmacokinetics of Melphalan in Patients with Multiple Myeloma Undergoing High Dose Therapyen
dc.typeJournal Articleen
dc.identifier.journaltitleBritish Journal of Clinical Pharmacologyen
dc.type.studyortrialMulticentre Studiesen
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
Appears in Collections:Oncology / Cancer
Show simple item record

Page view(s)

checked on Mar 23, 2023

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.