Add time:08/05/2019         Source:sciencedirect.com

Dibromodulcitol (DBD), labelled with [3−H] at position C-1, was administered orally to 6 patients in a single dose of 15 mg/kg. Kinetic parameters were calculated for the effective drug (DBD + BrEpG + DAG), protein-bound hexitol moieties and free metabolites. Approximate values were estimated for the oral bioavailability of DBD. Disposal of the drug by metabolism and excretion was described by a simplified catenary model. The results indicated that 8–20% of the drug became firmly bound to macromolecules, probably by alkylation. The slow rate of alkylation in vivo (half-life 14 hr) may imply conversion of DBD into epoxides and their alkylating interaction with the target nucleofiles. The long retention of the firmly bound hexitol moieties in the body may be an indicator of the cumulative potency of DBD and must be taken into consideration by developing dosage schedules.

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