Document Detail


A pharmacokinetic study of plerixafor in subjects with varying degrees of renal impairment.
MedLine Citation:
PMID:  19748593     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Plerixafor is a selective antagonist of CXCR4 used for mobilization of hematopoietic stem cells (HSCs) for autologous stem cell transplantation (SCT) in patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). This Phase 1 open-label study in healthy subjects was conducted to evaluate the pharmacokinetic characteristics of plerixafor in subjects with renal impairment. All subjects received a single 0.24 mg/kg subcutaneous dose of plerixafor. Subjects were stratified into 4 cohorts based on creatinine clearance determined from a 24-hour urine collection: control (>90 mL/min), mild renal impairment (51-80 mL/min), moderate renal impairment (31-50 mL/min), and severe renal impairment (<31 mL/min, not requiring dialysis). Eleven female subjects (48%) and 12 male subjects (52%), ranging in age from 35 to 73 years, were enrolled. Plerixafor clearance was reduced in subjects with renal impairment and was positively correlated with creatinine clearance. The mean area under the concentration- versus-time curve from time 0 to 24 hours postdose of plerixafor in subjects with mild, moderate, and severe renal impairment was 7%, 32%, and 39% higher, respectively, than that in subjects with normal renal function. Renal impairment had no effect on maximal plasma concentrations. The safety profile was similar among subjects with renal impairment and controls. No renal impairment-related trends in the incidence of adverse events were apparent. A plerixaflor dose reduction to 160 microg/kg in patients with a creatinine clearance value <or= 50 mL/min is expected to result in exposure similar to that in patients with normal to mildly impaired renal function.
Authors:
Ronald MacFarland; Marjie L Hard; Robert Scarborough; Karin Badel; Gary Calandra
Related Documents :
9610573 - Renal tubular dysfunction in patients with cystic disease of the kidneys.
6638543 - Comparative renal effects of midazolam and thiopental in humans.
9610573 - Renal tubular dysfunction in patients with cystic disease of the kidneys.
Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-10
Journal Detail:
Title:  Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation     Volume:  16     ISSN:  1523-6536     ISO Abbreviation:  Biol. Blood Marrow Transplant.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-07     Completed Date:  2010-03-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9600628     Medline TA:  Biol Blood Marrow Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  95-101     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Affiliation:
Genzyme Corp, Cambridge, Massachusetts, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Cohort Studies
Creatinine / metabolism,  urine
Female
Hematopoietic Stem Cell Mobilization
Heterocyclic Compounds / adverse effects,  blood,  pharmacokinetics*,  urine
Humans
Kidney Function Tests
Male
Metabolic Clearance Rate
Middle Aged
Receptors, CXCR4 / antagonists & inhibitors*
Renal Insufficiency / blood,  metabolism*,  physiopathology,  urine
Chemical
Reg. No./Substance:
0/Heterocyclic Compounds; 0/Receptors, CXCR4; 155148-31-5/JM 3100; 60-27-5/Creatinine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  N-Nitrosopiperidine and N-Nitrosodibutylamine induce apoptosis in HepG2 cells via the caspase depend...
Next Document:  Nutritional epidemiology in the context of nitric oxide biology: A risk-benefit evaluation for dieta...