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Preclinical pharmacokinetic and toxicology assessment of red blood cells prepared with S‐303 pathogen inactivation treatment
Author(s) -
North Anne,
Ciaravino Vic,
Mufti Nina,
Corash Laurence
Publication year - 2011
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2011.03132.x
Subject(s) - toxicity , pharmacokinetics , toxicokinetics , pharmacology , medicine , white blood cell , red blood cell , blood product , whole blood , hematology , immunology , surgery
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. STUDY DESIGN AND 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. CONCLUSION: 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.