Elena Gras-Colomer1,2, María Amparo Martínez-Gómez3,4, Ana Moya-Gil3, Miguel Fernandez-Zarzoso5, Matilde Merino-Sanjuan6,7, Mónica Climente-Martí3,6. 1. Pharmacy Service, Hospital Universitario Dr. Peset, Avenida Gaspar Aguilar, 90, 46017, Valencia, Spain. gras_ele@gva.es. 2. FISABIO, Hospital Universitario Dr. Peset, Valencia, Spain. gras_ele@gva.es. 3. Pharmacy Service, Hospital Universitario Dr. Peset, Avenida Gaspar Aguilar, 90, 46017, Valencia, Spain. 4. FISABIO, Hospital Universitario Dr. Peset, Valencia, Spain. 5. Hematology Service, Hospital Universitario Dr. Peset, Valencia, Spain. 6. Pharmacy and Pharmaceutical Technology Department, Universidad de Valencia, Valencia, Spain. 7. Molecular Recognition and Technological Development Institute, Centro Mixto Universidad Politécnica de Valencia, Universidad de Valencia, Valencia, Spain.
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.
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.
Authors: E Gras Colomer; M A Martínez Gómez; A González Alvarez; M Climente Martí; P León Moreno; M Fernández Zarzoso; N V Jiménez-Torres Journal: J Pharm Biomed Anal Date: 2014-01-03 Impact factor: 3.935
Authors: Judith Blanz; Johann Groth; Christina Zachos; Christina Wehling; Paul Saftig; Michael Schwake Journal: Hum Mol Genet Date: 2009-11-20 Impact factor: 6.150
Authors: M L Figueroa; B E Rosenbloom; A C Kay; P Garver; D W Thurston; J A Koziol; T Gelbart; E Beutler Journal: N Engl J Med Date: 1992-12-03 Impact factor: 91.245
Authors: P S Kishnani; M DiRocco; P Kaplan; A Mehta; G M Pastores; S E Smith; A C Puga; R M Lemay; N J Weinreb Journal: Mol Genet Metab Date: 2009-02-04 Impact factor: 4.797