ArticleBritish journal of clinical pharmacology2010
Population pharmacokinetics of melphalan in patients with multiple myeloma undergoing high dose therapy.
Article in British journal of clinical pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 77 citations in OpenAlex.
- Lentiviral gene therapy with reduced-intensity conditioning for sickle cell disease: a phase 1/2 trial.Nature medicine · 2025Trial
- A new parameter in multiple myeloma: CYP3A4*1B single nucleotide polymorphism.Annals of hematology · 2021Trial
- Cryotherapy as prophylaxis against oral mucositis after high-dose melphalan and autologous stem cell transplantation for myeloma: a randomised, open-label, phase 3, non-inferiority trial.Bone marrow transplantation · 2019Trial
- Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial.The Lancet. Haematology · 2019Trial
- Final outcomes of escalated melphalan 280 mg/mBone marrow transplantation · 2019Trial
- Lower glomerular filtration rate predicts increased hepatic and mucosal toxicity in myeloma patients treated with high-dose melphalan.International journal of hematology · 2018Trial
- Population Pharmacokinetics and Optimal Sampling Strategy for Model-Based Precision Dosing of Melphalan in Patients Undergoing Hematopoietic Stem Cell Transplantation.Clinical pharmacokinetics · 2018Trial
- Melphalan 140 mg/mHaematologica · 2018Trial
- Associations of High-Dose Melphalan Pharmacokinetics and Outcomes in the Setting of a Randomized Cryotherapy Trial.Clinical pharmacology and therapeutics · 2017Trial
- First-in-human, phase I/IIa clinical study of the peptidase potentiated alkylator melflufen administered every three weeks to patients with advanced solid tumor malignancies.Investigational new drugs · 2015Trial
- A Simulation-Based Assessment of Dosage Regimen Appropriateness for Multiple Myeloma Medicines Reflecting Demographic and Ethnic Differences.Clinical and translational science · 2026Article
- Accuracy of Real-Time PK-Guided Melphalan Dosing in Achieving Target Exposure in Myeloma Patients Undergoing Autologous Transplant.Pharmaceutics · 2026Article
- [Efficacy and safety of oral melphalan as conditioning regimen for autologous hematopoietic stem cell transplantation in multiple myeloma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Article
- Population Pharmacokinetics of Melphalan in Pediatric Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation with Various Conditioning Regimens.European journal of drug metabolism and pharmacokinetics · 2026Article
- Optimizing high dose melphalan.Blood reviews · 2024Review
- The Impact of Renal Impairment in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation With Melphalan Conditioning.Journal of hematology · 2023Article
- Anti-Angiogenic Activity of Drugs in Multiple Myeloma.Cancers · 2023Review
- Challenges associated with test dose pharmacokinetic predictions of high dose melphalan exposure in patients with multiple myeloma.European journal of clinical pharmacology · 2022Article
- Relationship of iothalamate clearance and NRM in patients receiving fludarabine and melphalan reduced-intensity conditioning.Blood advances · 2022Article
- Population Pharmacokinetics of Melphalan in a Large Cohort of Autologous and Allogeneic Hematopoietic Cell Transplantation Recipients: Towards Individualized Dosing Regimens.Clinical pharmacokinetics · 2022Article
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo 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.
methodsPopulation 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.
resultsA 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.
conclusionsCreatinine 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.
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