Cellular Uptake of Glucocerebrosidase in Gaucher Patients Receiving Enzyme Replacement Treatment
Por:
Gras-Colomer, E, Amparo Martinez-Gomez, M, Moya-Gil, A, Fernandez-Zarzoso, M, Merino-Sanjuan, M and Climente-Marti, M
Publicada:
1 sep 2016
Resumen:
Background Enzyme replacement therapy (ERT) is currently the standard treatment for patients with Gaucher disease type I (GD1), but the pharmacokinetics have hardly been studied. This study aimed to quantify in vivo enzyme activity in peripheral leukocytes from patients receiving long-term treatment with imiglucerase or velaglucerase for GD1, and set out to assess the process of enzymatic uptake by peripheral leukocytes.
Methods A prospective semi-experimental study was conducted. Four time points for blood withdrawal were planned per patient to quantify the intra-leukocyte enzymatic activity. In order to assess the uptake process, the rate of enzyme uptake by leukocytes (Rupt) and the rate of enzyme disappearance from the plasma (Rdis) were estimated.
Results Eight GD1 patients were included. Intra-leukocyte activity was 24.31 mU/mL [standard deviation (SD) 6.32 mU/mL; coefficient of variation (CV) 25.96 %] at baseline and 27.14 mU/mL (SD 6.96 mU/mL; CV 25.65 %) at 15 min post-perfusion. The relationships with the administered dose were linear. The Rupt value was 37.73 mU/mL/min [95 % confidence interval (CI) 25.63-49.84] and showed a linear correlation with the administered enzyme dose (p < 0.05), and the Rdis value was 189.43 mU/mL/min (95 % CI 80.31-298.55) and also showed a linear correlation with the dose (p < 0.05).
Conclusion This was the first in vivo study to quantify the accumulated enzymatic activity in patients receiving ERT for GD1. It showed that intra-leukocyte activity at baseline and at 15 min post-perfusion could be used as a possible marker for therapeutic individualization in patients receiving ERT for GD1.
Filiaciones:
:
Hosp Univ Dr Peset, Serv Pharm, Ave Gaspar Aguilar 90, Valencia 46017, Spain
Hosp Univ Dr Peset, FISABIO, Valencia, Spain
:
Hosp Univ Dr Peset, Serv Pharm, Ave Gaspar Aguilar 90, Valencia 46017, Spain
Hosp Univ Dr Peset, FISABIO, Valencia, Spain
:
Hosp Univ Dr Peset, Serv Pharm, Ave Gaspar Aguilar 90, Valencia 46017, Spain
:
Hosp Univ Dr Peset, Hematol Serv, Valencia, Spain
Merino-Sanjuan, M:
Univ Valencia, Pharm & Pharmaceut Technol Dept, Valencia, Spain
Univ Valencia, Ctr Mixto Univ Politecn Valencia, Mol Recognit & Technol Dev Inst, Valencia, Spain
:
Hosp Univ Dr Peset, Serv Pharm, Ave Gaspar Aguilar 90, Valencia 46017, Spain
Univ Valencia, Pharm & Pharmaceut Technol Dept, Valencia, Spain
|