title: Pharmacokinetics of Novel Plant Cell-Expressed Taliglucerase Alfa in Adult and Pediatric Patients with Gaucher Disease.
abstract: Taliglucerase alfa is a beta-glucocerebrosidase enzyme replacement therapy approved in the United States, Israel, and other countries for treatment of Type 1 Gaucher disease in adults, and is the first approved plant cell--expressed recombinant protein. In this report, taliglucerase alfa pharmacokinetics were assessed in adult and pediatric patients with Gaucher disease from separate multicenter trials of 30 Units/kg and 60 Units/kg doses infused every 2 weeks. Serial blood samples were obtained from adult patients following single-dose administration on day 1 (n = 26) and multiple doses at week 38 (n = 29), and from pediatric patients following administration of multiple doses of taliglucerase alfa for 10-27 months (n = 10). In both adult and pediatric patients, maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time zero to last measureable concentration (AUC0-t), and from time zero to infinity (AUC0-∞) were higher after 60 Units/kg dose than 30 Units/kg dose. No tendency for accumulation or change in taliglucerase alfa pharmacokinetic parameters over time from day 1 to week 38 was observed with repeated doses of 30 or 60 Units/kg in adults. After multiple doses, mean (range) dose-normalized pharmacokinetic parameters were similar for adult versus pediatric patients receiving 60 Units/kg: Cmax expressed in ng/mL/mg was 42.4 (14.5-95.4) in adults and 46.6 (34.4-68.4) in pediatric patients, AUC0 t expressed in ng • h/mL/mg was 63.4 (26.3-156) in adults and 63.9 (39.8-85.1) in pediatric patients, t1/2 expressed in minutes was 34.8 (11.3-104) in adults and 31.5 (18.0-42.9) in pediatric patients and total body clearance expressed in L/h was 19.9 (6.25-37.9) in adults and 17.0 (11.7-24.9) in pediatric patients. These pharmacokinetic data extend the findings of taliglucerase alfa in adult and pediatric patients.
  
  
  BACKGROUND
  ClinicalTrials.gov. NCT00376168 (in adults); NCT01411228 (in children).
authors.affiliation: Pfizer, New York, NY, United States of America.
authors.forename: Richat
authors.initials: R
authors.lastname: Abbas
authors.affiliation: Target Health, New York, NY, United States of America.
authors.forename: Glen
authors.initials: G
authors.lastname: Park
authors.affiliation: Pfizer, New York, NY, United States of America.
authors.forename: Bharat
authors.initials: B
authors.lastname: Damle
authors.affiliation: Protalix Biotherapeutics, Carmiel, Israel.
authors.forename: Raul
authors.initials: R
authors.lastname: Chertkoff
authors.affiliation: Protalix Biotherapeutics, Carmiel, Israel.
authors.forename: Sari
authors.initials: S
authors.lastname: Alon
mesh_terms: D000328:Adult; D002648:Child; D003710:Demography; D004305:Dose-Response Relationship, Drug; D005260:Female; D005776:Gaucher Disease / Q000097:blood / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D059828:Plant Cells / Q000378:metabolism*
chemical_list: D005962:Glucosylceramidase; C582473:taliglucerase alfa