ORIGINAL RESEARCH ARTICLE Cellular Uptake of Glucocerebrosidase in Gaucher Patients Receiving Enzyme Replacement Treatment Elena Gras-Colomer 1,2 • Marı ´a Amparo Martı ´nez-Go ´mez 1,2 • Ana Moya-Gil 1 • Miguel Fernandez-Zarzoso 3 • Matilde Merino-Sanjuan 4,5 • Mo ´nica Climente-Martı ´ 1,4 Ó Springer International Publishing Switzerland 2016 Abstract Background Enzyme replacement therapy (ERT) is cur- rently 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 con- ducted. 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 disap- pearance from the plasma (Rdis) were estimated. Results Eight GD1 patients were included. Intra-leuko- cyte 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. Key Points Quantification of enzymatic activity in leukocytes could be used as a marker for therapeutic individualization in patients receiving enzyme replacement therapy for Gaucher disease type I. The rate of enzyme disappearance from the plasma and the rate of enzyme uptake by leukocytes show a linear correlation with the administered enzyme dose and high inter-patient variability. After administration of imiglucerase or velaglucerase, the leukocyte enzymatic activity values and rates of internalization by leukocytes are similar. 1 Introduction Gaucher disease (GD) is the most frequent enzyme defi- ciency-associated disorder among the inherited lysosome storage diseases, with an overall prevalence of 1 per & Elena Gras-Colomer gras_ele@gva.es 1 Pharmacy Service, Hospital Universitario Dr. Peset, Avenida Gaspar Aguilar, 90, 46017 Valencia, Spain 2 FISABIO, Hospital Universitario Dr. Peset, Valencia, Spain 3 Hematology Service, Hospital Universitario Dr. Peset, Valencia, Spain 4 Pharmacy and Pharmaceutical Technology Department, Universidad de Valencia, Valencia, Spain 5 Molecular Recognition and Technological Development Institute, Centro Mixto Universidad Polite ´cnica de Valencia, Universidad de Valencia, Valencia, Spain Clin Pharmacokinet DOI 10.1007/s40262-016-0387-2