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Journal of Inherited Metabolic Disease

, Volume 32, Supplement 1, pp 253–258 | Cite as

Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs

  • M. B. Passage
  • A. W. Krieger
  • M. C. Peinovich
  • T. Lester
  • S. Q. Le
  • P. I. Dickson
  • E. D. Kakkis
SHORT REPORT

Summary

Intravenous enzyme replacement therapy with recombinant human α-l-iduronidase (rhIDU) is used weekly to treat mucopolysaccharidosis (MPS) I. We tested continuous administration of rhIDU at two dosing levels (0.58 mg/kg per week and 2 mg/kg per week) in MPS I dogs, and compared the efficacy of continuous infusion with the clinically used 0.58 mg/kg weekly three-hour infusion. Peak plasma concentrations of rhIDU were much higher in weekly-treated dogs (mean 256 units/ml) than steady-state concentrations in dogs treated with continuous infusion (mean 1.97 units/ml at 0.58 mg/kg per week; 8.44 units/ml at 2 mg/kg per week). Dogs receiving continuous IV rhIDU, even at a higher (2 mg/kg per week) dose, had consistently lower iduronidase levels in tissues than dogs receiving a weekly (0.58 mg/kg per week) dose. GAG storage was also less improved by continuous intravenous infusion. Adverse events were similar in all dosing groups. We found that continuous administration of 2 mg/kg per week rhIDU to MPS I dogs was insufficient to achieve GAG storage reduction comparable to 0.58 mg/kg weekly dosing.

Keywords

Continuous Infusion Enzyme Replacement Therapy Fabry Disease Disease Gauche Weekly Dose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ERT

enzyme replacement therapy

GAG

glycosaminoglycan

MPS

mucopolysaccharidosis

rhIDU

recombinant human α-l-iduronidase

Notes

Acknowledgements

Funding was provided by the Ryan Foundation for MPS Children and BioMarin Pharmaceutical Inc. Thanks to Michael McEntee, Rita Esquivel, and Dan Garner for their technical assistance. Thanks to Paul Fu, Sr, for measurement of urinary creatinine.

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • M. B. Passage
    • 1
  • A. W. Krieger
    • 1
  • M. C. Peinovich
    • 1
  • T. Lester
    • 2
  • S. Q. Le
    • 1
  • P. I. Dickson
    • 1
  • E. D. Kakkis
    • 2
  1. 1.Los Angeles Biomedical Research Institute at HarborUCLATorranceUSA
  2. 2.BioMarin Pharmaceutical Inc.NovatoUSA

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