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The absorption and metabolism of dibromodulcitol in patients with advanced cancer
Author(s) -
Belej M. A.,
Troetel W. M.,
Weiss A. J.,
Stambaugh J. E.,
Manthei R. W.
Publication year - 1972
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1972134563
Subject(s) - urine , chemistry , metabolism , absorption (acoustics) , drug , gastrointestinal tract , excretion , chromatography , medicine , pharmacology , biochemistry , physics , acoustics
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.