Structure Elucidation and Biological Activity of the Oversulfated Chondroitin Sulfate Contaminant in Baxter Heparin
| Autor: | Shawn F. Bairstow, Jeff McKee, Ton That Hai, Todd Wielgos, Christina M. Szabo, Nelly Viseux, Mark Nordhaus, Jon N. Cammack, Norbert Riedel, Ed Chess, Joe Ray, Shane Donovan, Peifeng Hu, Richard J. Johnson, Jennifer Campbell |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Magnetic Resonance Spectroscopy Swine Pharmacology Immunoenzyme Techniques Rats Sprague-Dawley chemistry.chemical_compound Sulfation medicine Animals Pharmacology (medical) Chondroitin sulfate Bradykinin receptor Heparin Chemistry Chondroitin Sulfates Antagonist Anticoagulants Biological activity Kallikrein Rats De novo synthesis Biochemistry Kallikreins Hypotension Drug Contamination medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 50:1159-1170 |
| ISSN: | 0091-2700 |
| DOI: | 10.1177/0091270009355158 |
| Popis: | From late December 2007 to February 2008, the number of adverse responses to heparin infusions rose noticeably above baseline levels in North America, ultimately resulting in a widespread recall of all heparin vial products made by Baxter Healthcare. Using various analytical techniques and the de novo synthesis of a fully sulfated chondroitin sulfate (FSCS) derivative, the authors have confirmed the identity of the contaminant as an oversulfated chondroitin sulfate (OSCS) and have also defined the heterogeneity and concentration of this contaminant in various lots of heparin. Using both contaminated heparin products and the synthetically produced derivative, the authors have shown that the OSCS produces a dose-dependent hypotension in both pigs and rats and that the response in rats can be abrogated with bradyzide, a rodent-selective B(2) bradykinin receptor antagonist. The no observed effect level (NOEL) for this contaminant appears to be approximately 1 mg/kg, corresponding to a contamination level in finished lots of heparin of approximately 3%. Using human plasma, the OSCS derivative was shown to activate kallikrein. These data provide insight into the etiology of the adverse events, particularly refractory hypotension, observed in patients who were exposed to heparin contaminated with OSCS. |
| Databáze: | OpenAIRE |
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