The absorption and metabolism of dibromodulcitol in patients with advanced cancer

Abstract

In patients with advanced cancer 14 C‐Dibromodulcitol (DBD) was rapidly absorbed from the gastrointestinal tract, entered the systemic circulation within 15 minutes after administration, and reached a maximum blood level within one hour. Plasma half‐life of carbon‐14 compounds was 8 hours. The drug was readily hydrolyzed in the plasma to monobromodulcitol and various epoxides so that within 2 hours after administration, less than 5 per cent of the unchanged drug remained. 14 C‐DBD compounds entered spinal, pleural, and ascitic fluids and reached a maximum concentration in 5 hours. Biopsy specimens indicated that DBD was present in both normal and malignant tissues. In autopsy specimens, radioactivity equivalent to 1 to 4 p.g of drug per gram of tissue was detectable for as long as 6 days after administration. Renal excretion was the only apparent route of elimination of 14 C‐DBD, since neither expired and metabolites was rapid; 68 to 79 per cent of the administered radioactivity appeared in the urine within 48 hours. Chromatography of urine indicated the presence of unchanged DBD as well as 7 metabolic products.The metabolites tentatively identified are: monobromodulcitol; a diepoxy derivative, 1,2‐5,6‐dianhydrodulcitol; an epoxide, anhydrodulcitol; dulcitol; and bromide ion. Two products remain unidentified.