title: Preclinical pharmacokinetic and toxicology assessment of red blood cells prepared with S-303 pathogen inactivation treatment.
abstract: BACKGROUND
  A system has been developed to inactivate a wide spectrum of blood-borne pathogens in red blood cells (RBCs) before transfusion. The system utilizes S-303 to target nucleic acids of pathogens and white blood cells. The safety of pathogen inactivated RBC was assessed using S-303-treated RBCs (S-303 RBCs) and S-300, the primary degradation product of S-303.
  
  
  METHODS
  As part of a preclinical safety evaluation program, intravenous toxicity, safety pharmacology, toxicokinetic, and pharmacokinetic studies were conducted in rats and dogs with S-303 RBCs and S-300.
  
  
  RESULTS
  Single and repeated transfusions of S-303 RBCs were well tolerated in rats and dogs at S-303 concentrations up to five times higher than that used to prepare RBCs for clinical use. For S-300, the doses ranged from the lowest level representative of a clinical exposure from transfusion of 1 unit (0.052 mg/kg/day) to up to the amount of S-300 that would result from exposure to more than 1900 units of RBCs (100 mg/kg/day). There were no related effects of S-303 RBCs or S-300 on mortality, clinical status, body weight, or clinical laboratory assessments and no evidence of organ toxicity. S-300 did not accumulate in the plasma of rats and dogs after repeated transfusions. For all the studies, plasma S-303 was consistently below the limit of quantitation.
  
  
  CONCLUSIONS
  The level of residual S-303 and S-300 in the treated blood component is well below that at which no adverse effects were observed. These results support further clinical development of S-303 RBCs for prevention of transfusion-transmitted infections.
authors: Department of Development and Clinical Research and Medical Affairs, Cerus Corp., Concord, California, USA. anorth@cerus.com
authors: Anne
authors: A
authors: North
authors: Vic
authors: V
authors: Ciaravino
authors: Nina
authors: N
authors: Mufti
authors: Laurence
authors: L
authors: Corash
mesh_terms: D000166:Acridines / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000633:toxicity; D058731:Blood Safety; D017848:Blood-Borne Pathogens / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D005260:Female; D008297:Male; D009588:Nitrogen Mustard Compounds / Q000097:blood* / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D018675:Toxicity Tests
chemical_list: C506266:(N,N-bis(2-chloroethyl))-2-aminoethyl-3-((acridin-9-yl)amino)propionate; D000166:Acridines; D000890:Anti-Infective Agents; D009588:Nitrogen Mustard Compounds