Metabolism of chloramphenicol succinate in human bone marrow

Objective/methods: The metabolism of chloramphenicol succinate (CAPS) by hu man bone marrow was studied in vitro using 75 marrow samples. Whole marrow samples were incubated with CAPS with or without reduced nicotinamide adeni ne dinucleotide phosphate for 1, 2 and 3 h at 37 degrees C. Ficoll-paque-se parated marrow mononuclear cells and erythrocytes were similarly incubated. After precipitation and centrifugation, clear supernatant was analysed for the presence of metabolites using high-performance liquid chromatography. Results: Only one metabolite was detected when CAPS was incubated for 3 h w ith whole marrow from 72 donors. Its retention time (RT 10.9 min) correspon ded to chloramphenicol (CAP). When CAPS was incubated with samples of whole marrow, marrow mononuclear cells, marrow erythrocytes, marrow plasma and p eripheral blood from one donor who had taken Traditional Chinese Medicine ( TCM), three metabolite peaks were detected within 15 min to 1 h. The RT of two of these peaks corresponded to CAP and nitroso-CAP (RT 14.9 min), but o ne peak remained unidentified. These peaks were not detected in the control samples incubated without CAPS. Blood samples collected after 3 months and 6 months to reconfirm metabolic activity yielded no such metabolite peaks when incubated with CAPS for 1-3 h. Therefore induction of enzyme activity by TCM was suspected. Three metabolite peaks with the same RTs were also de tected when CAPS was incubated for 3 h with whole marrow from two other don ors. Conclusion: These studies demonstrated that CAPS may be metabolised to CAP and occasionally other metabolites in human bone marrow. This novel observa tion is particularly important because the bone marrow is known to be a tar get organ for chloramphenicol toxicity.