title: Cellular Uptake of Glucocerebrosidase in Gaucher Patients Receiving Enzyme Replacement Treatment.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Pharmacy Service, Hospital Universitario Dr. Peset, Avenida Gaspar Aguilar, 90, 46017, Valencia, Spain. gras_ele@gva.es.|FISABIO, Hospital Universitario Dr. Peset, Valencia, Spain. gras_ele@gva.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Gras-Colomer
authors.affiliation: Pharmacy Service, Hospital Universitario Dr. Peset, Avenida Gaspar Aguilar, 90, 46017, Valencia, Spain.|FISABIO, Hospital Universitario Dr. Peset, Valencia, Spain.
authors.forename: María Amparo
authors.initials: MA
authors.lastname: Martínez-Gómez
authors.affiliation: Pharmacy Service, Hospital Universitario Dr. Peset, Avenida Gaspar Aguilar, 90, 46017, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Moya-Gil
authors.affiliation: Hematology Service, Hospital Universitario Dr. Peset, Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernandez-Zarzoso
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, Universidad de Valencia, Valencia, Spain.|Molecular Recognition and Technological Development Institute, Centro Mixto Universidad Politécnica de Valencia, Universidad de Valencia, Valencia, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Merino-Sanjuan
authors.affiliation: Pharmacy Service, Hospital Universitario Dr. Peset, Avenida Gaspar Aguilar, 90, 46017, Valencia, Spain.|Pharmacy and Pharmaceutical Technology Department, Universidad de Valencia, Valencia, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Climente-Martí
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D056947:Enzyme Replacement Therapy / Q000379:methods*; D005260:Female; D005776:Gaucher Disease / Q000201:enzymology* / Q000378:metabolism / Q000628:therapy*; D005962:Glucosylceramidase / Q000187:drug effects / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D005962:Glucosylceramidase; C550184:Velaglucerase alfa, human; C090568:imiglucerase