A pharmacokinetic study of plerixafor in subjects with varying degrees of renal impairment.
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.
MacFarland
Ronald
R
Genzyme Corp, Cambridge, Massachusetts, USA.
Hard
Marjie L
ML
Scarborough
Robert
R
Badel
Karin
K
Calandra
Gary
G
D000328:Adult; D000368:Aged; D001596:Benzylamines; D015331:Cohort Studies; D003404:Creatinine / Q000378:metabolism / Q000652:urine; D000080027:Cyclams; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006571:Heterocyclic Compounds / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D051437:Renal Insufficiency / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine
D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D003404:Creatinine; C088327:plerixafor