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Cellular Uptake of Glucocerebrosidase in Gaucher Patients Receiving Enzyme Replacement Treatment

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Abstract

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.

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Acknowledgments

We thank the patients with GD and health care personnel from Pharmacy and Hematology Service.

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Authors and Affiliations

  1. Pharmacy Service, Hospital Universitario Dr. Peset, Avenida Gaspar Aguilar, 90, 46017, Valencia, Spain

    Elena Gras-Colomer, María Amparo Martínez-Gómez, Ana Moya-Gil & Mónica Climente-Martí

  2. FISABIO, Hospital Universitario Dr. Peset, Valencia, Spain

    Elena Gras-Colomer & María Amparo Martínez-Gómez

  3. Hematology Service, Hospital Universitario Dr. Peset, Valencia, Spain

    Miguel Fernandez-Zarzoso

  4. Pharmacy and Pharmaceutical Technology Department, Universidad de Valencia, Valencia, Spain

    Matilde Merino-Sanjuan & Mónica Climente-Martí

  5. Molecular Recognition and Technological Development Institute, Centro Mixto Universidad Politécnica de Valencia, Universidad de Valencia, Valencia, Spain

    Matilde Merino-Sanjuan

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  1. Elena Gras-Colomer
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  2. María Amparo Martínez-Gómez
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  6. Mónica Climente-Martí
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Corresponding author

Correspondence to Elena Gras-Colomer.

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Conflict of interest

Elena Gras-Colomer, María Amparo Martínez-Gómez, Ana Moya-Gil, Miguel Fernandez-Zarzoso, Matilde Merino-Sanjuan and Mónica Climente-Martí have no conflicts of interest that might be relevant to the content of this manuscript.

Funding

This work was supported by Foundation for the Promotion of Health and Biomedical Research in the Valencian Community (FISABIO).

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Gras-Colomer, E., Martínez-Gómez, M.A., Moya-Gil, A. et al. Cellular Uptake of Glucocerebrosidase in Gaucher Patients Receiving Enzyme Replacement Treatment. Clin Pharmacokinet 55, 1103–1113 (2016). https://doi.org/10.1007/s40262-016-0387-2

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  • DOI: https://doi.org/10.1007/s40262-016-0387-2

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