Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs.
J Inherit Metab Dis
; 32 Suppl 1: S253-8, 2009 Dec.
Article
en En
| MEDLINE
| ID: mdl-19562502
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mucopolisacaridosis I
/
Terapia de Reemplazo Enzimático
/
Iduronidasa
Tipo de estudio:
Evaluation_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Inherit Metab Dis
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos