title: Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease.
abstract: BACKGROUND
  Fabry disease (FD) is caused by an X-linked deficiency in the activity of alpha-galactosidase A and the resultant accumulation of globotriaosylceramide (Gb3) in multiple tissues. Nearly all classically affected males with FD experience kidney dysfunction, with progression to end-stage renal disease (ESRD) in the third decade of life or shortly thereafter.
  
  
  METHODS
  Twenty-two FD patients (20 men and 2 women) receiving dialysis or who had a history of kidney transplantation were treated with agalsidase alfa in an open label setting using the same dosing regimen given to patients without ESRD (0.2 mg/kg every other week). Pharmacokinetics (PK) were determined during and following the initial dose, and safety was evaluated during therapy. Change in plasma Gb3 level was used as a surrogate marker of enzyme activity in vivo.
  
  
  RESULTS
  A typical biphasic plasma elimination profile was seen in both dialysis and transplant patients, similar to that observed in 18 non-ESRD FD patients. Calculated PK parameters were similar to the three patient groups. In the male patients, plasma Gb3 level declined by 43% after 6 months (P<0.001). Infusion reactions were experienced by 8 of 21 (38%) patients, but did not result in any infusions being stopped prematurely. Anti-agalsidase alfa IgG antibodies were detected in 15.8% of males and 0% female patients. No anti-agalsidase alfa IgE antibodies were detected.
  
  
  CONCLUSIONS
  The same dosing regimen of agalsidase alfa may be safely administered to FD patients with ESRD as given to those without ESRD.
authors: Department of Neurology, New York University School of Medicine, 403 East 34th Street, New York, NY 10016, and St. Louis Children's Hospital, MO, USA. gregory.pastores@med.nyu.edu
authors: Gregory M
authors: GM
authors: Pastores
authors: Ellen
authors: E
authors: Boyd
authors: Kerry
authors: K
authors: Crandall
authors: Alison
authors: A
authors: Whelan
authors: Linda
authors: L
authors: Piersall
authors: Natalie
authors: N
authors: Barnett
mesh_terms: D000328:Adult; D000368:Aged; D000795:Fabry Disease / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007527:Isoenzymes / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis; D013997:Time Factors; D014281:Trihexosylceramides / Q000097:blood; D000519:alpha-Galactosidase / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D007074:Immunoglobulin G; D007527:Isoenzymes; D011994:Recombinant Proteins; D014281:Trihexosylceramides; C000627036:agalsidase alfa; C018549:globotriaosylceramide; D000519:alpha-Galactosidase