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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)S253-S258
JournalJournal of Inherited Metabolic Disease
Volume32
Issue numberSUPPL. 1
DOIs
StatePublished - Dec 2009

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