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Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs
Author(s) -
Passage M. B.,
Krieger A. W.,
Peinovich M. C.,
Lester T.,
Le S. Q.,
Dickson P. I.,
Kakkis E. D.
Publication year - 2009
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-009-1198-5
Subject(s) - medicine , dosing , enzyme replacement therapy , adverse effect , pharmacokinetics , continuous infusion , anesthesia , urology , disease
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.