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- Title
Cellular Uptake of Glucocerebrosidase in Gaucher Patients Receiving Enzyme Replacement Treatment.
- Authors
Gras-Colomer, Elena; Martínez-Gómez, María; Moya-Gil, Ana; Fernandez-Zarzoso, Miguel; Merino-Sanjuan, Matilde; Climente-Martí, Mónica; Martínez-Gómez, María Amparo; Climente-Martí, Mónica
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusion: </bold>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.
- Subjects
GAUCHER'S disease; GAUCHER'S disease treatment; PHARMACOKINETICS; LEUCOCYTES; DRUG administration; PATIENTS; DRUG therapy; GLYCOSIDASES; LONGITUDINAL method; THERAPEUTICS
- Publication
Clinical Pharmacokinetics, 2016, Vol 55, Issue 9, p1103
- ISSN
0312-5963
- Publication type
Academic Journal
- DOI
10.1007/s40262-016-0387-2