Bioavailability of sodium cyanate in patients with sickle cell disease and the lack of inhibition in vitro of globin synthesis at in vivo concentrations of cyanate.
Studies have been made on the bioavailability in blood of sodium cyantate administered orally in gelatin capsules, in gelatin capsules plus antacid, in enteric-coated capsules and in cocoa butter suppositories administered rectally to patients with sickle cell disease. Maximal blood concentrations of cyanate did not exceed 0.4 mM. Sodium cyanate taken orally in gelatin capsules yielded the highest blood concentrations of the drug, but the peak concentrations and curve areas were not necessarily dose-related. The duration of the drug in the circulation was about 210 minutes. Administration of sodium cyanate in the gelatin capsules, taken with an antacid, improved the dose-response relationship within a given patient. Enteric-coated capsules and suppositories were found to show variable and low bioavailability profiles, respectively. Variability in bioavailability between patients with a given dosage form requires further study. Since the concentration of cyanate attainable in vivo does not inhibit synthesis of either the alpha- or beta-chain of hemoglobin in vitro, previous reports on the inhibitory effects of 10 to 100 mM cyanate on globin synthesis in vitro do not appear to be relevant.
D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000378:metabolism*; D000863:Antacids; D001682:Biological Availability; D002214:Capsules; D003485:Cyanates / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005780:Gelatin; D005914:Globins / Q000096:biosynthesis*; D006801:Humans; D013488:Suppositories; D013997:Time Factors
D000863:Antacids; D002214:Capsules; D003485:Cyanates; D013488:Suppositories; D005780:Gelatin; D005914:Globins