Pharmacokinetic-Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High-Dose Melphalan for Autologous Stem Cell Transplant.

08:00 EDT 20th October 2018 | BioPortfolio

Summary of "Pharmacokinetic-Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High-Dose Melphalan for Autologous Stem Cell Transplant."

High-dose melphalan (HDM) is part of the conditioning regimen in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT). However, individual sensitivity to melphalan varies, and many patients experience severe toxicities. Prolonged severe neutropenia is one of the most severe toxicities and contributes to potentially life-threatening infections and failure of ASCT. Granulocyte-colony stimulating factor (G-CSF) is given to stimulate neutrophil proliferation after melphalan administration. The aim of this study was to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model capable of predicting neutrophil kinetics in individual patients with MM undergoing ASCT with high-dose melphalan and G-CSF administration. The extended PK/PD model incorporated several covariates, including G-CSF regimen, stem cell dose, hematocrit, sex, creatinine clearance, p53 fold change, and race. The resulting model explained portions of interindividual variability in melphalan exposure, therapeutic effect, and feedback regulation of G-CSF on neutrophils, thus enabling simulation of various doses and prediction of neutropenia duration.


Journal Details

This article was published in the following journal.

Name: CPT: pharmacometrics & systems pharmacology
ISSN: 2163-8306


DeepDyve research library

PubMed Articles [34355 Associated PubMed Articles listed on BioPortfolio]

Population Pharmacokinetic-Pharmacodynamic Modeling of a Novel Methylphenidate Extended-Release Orally Disintegrating Tablet in Pediatric Patients With Attention-Deficit/Hyperactivity Disorder.

A methylphenidate (MPH) extended-release orally disintegrating tablet (MPH XR-ODT) formulation was recently approved for attention-deficit/hyperactivity disorder treatment in children 6 to 17 years of...

Propofol pharmacokinetic and pharmacodynamic profile and its electroencephalographic interaction with remifentanil in children.

Propofol and remifentanil are commonly combined during total intravenous anesthesia. The impact of remifentanil in this relationship is poorly quantified in children. Derivation of an integrated pharm...

Concizumab restores thrombin generation potential in patients with haemophilia: Pharmacokinetic/pharmacodynamic modelling results of concizumab phase 1/1b data.

Concizumab enhances thrombin generation (TG) potential in haemophilia patients by inhibiting tissue factor pathway inhibitor (TFPI). In EXPLORER3 (phase 1b), a dose-dependent pharmacokinetic/pharmacod...

Modified dose of melphalan-prednisone in multiple myeloma patients receiving bortezomib plus melphalan-prednisone treatment.

Bortezomib plus melphalan-prednisone (VMP) is a standard treatment for multiple myeloma, particularly for patients who are ineligible for high-dose therapy. However, early discontinuation or treatment...

Prophylaxis of Chemotherapy-induced Neutropenia and Febrile Neutropenia with Lipegfilgrastim in Patients with Non-Hodgkin Lymphoma (NADIR study).

The prospective non-interventional study (NIS) NADIR was designed to evaluate both effectiveness and safety of prophylactic use of lipegfilgrastim (Lonquex ), a glycopegylated granulocyte colony stimu...

Clinical Trials [9006 Associated Clinical Trials listed on BioPortfolio]

Immunosuppressive Therapy Optimization: Development of a Population Pharmacokinetic-pharmacodynamic (PK-PD) Model in Liver Transplantation

Prospective, non-randomized, open Pharmacokinetic-Pharmacogenetic-Pharmacodynamic monocentric study. Donor and recipient CYP3A5 genotype and recipient ABCB1 will not be communicate to clin...

Propofol Pharmacokinetics and Pharmacodynamics Modelling

The main purpose of this research is to develop a population pharmacokinetic and pharmacodynamic model of Propofol when used for induction and maintenance of anaesthesia, using BIS as a ph...

Pharmacokinetic/Pharmacodynamic Model of Propofol in Children

By measuring plasmatic concentration of propofol at different intervals during surgery of children aged 1 to 12 years old and measuring Bispectral Index (BIS) as a surrogate for cerebral a...

ANF-Rho in the Treatment of Chronic Neutropenia

A 6 month safety, tolerability, efficacy and pharmacokinetic study with ANF-Rho to treat patients with chronic neutropenia.

G-CSF in Preventing Neutropenia in Women Receiving Chemotherapy for Breast Cancer

RATIONALE: G-CSF may prevent or reduce febrile neutropenia in women receiving chemotherapy for breast cancer. It is not yet known which G-CSF regimen is more effective in preventing neutro...

Medical and Biotech [MESH] Definitions

A hematopoietic growth factor which promotes proliferation and maturation of neutrophil granulocytes. Clinically it is effective in decreasing the incidence of febrile neutropenia in patients with non-myeloid malignancies receiving myelosuppressive therapy or in reducing the duration of neutropenia and neutropenia-related clinical sequelae in patients with non-myeloid malignancies undergoing myeloblastive chemotherapy followed by BMT. It has also been used in AIDS patients with CMV retinitis being treated with GANCICLOVIR. (Gelman CR, Rumack BH & Hess AJ (eds): DRUGDEX(R) System. MICROMEDEX, Inc., Englewood, Colorado (Edition expires 11/30/95))

The presence of fungi circulating in the blood. Opportunistic fungal sepsis is seen most often in immunosuppressed patients with severe neutropenia or in postoperative patients with intravenous catheters and usually follows prolonged antibiotic therapy.

An asymptomatic and slow-growing PLASMA CELL dyscrasia characterized by presence of MYELOMA PROTEINS and clonal bone marrow plasma cells without end-organ damage (e.g., renal impairment). It is distinguished from MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE by a much higher risk of progression to symptomatic MULTIPLE MYELOMA.

Abnormal immunoglobulins characteristic of MULTIPLE MYELOMA.

Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.

Quick Search


DeepDyve research library

Relevant Topics

Stem Cells
Track and monitor developments in stem cell research and commercial development.  Follow the tabs above to read the latest global news, research, clinical trials on stem cells and follow companies active in the stem cell industry.  BioPort...

Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...

Searches Linking to this Article