Metabolism of chloramphenicol succinate in human bone marrow |
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Authors: | C S Ambekar B Cheung J Lee L C Chan R Liang C R Kumana |
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Institution: | (1) Departments of Medicine, Pathology and the Clinical Biochemistry Unit, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Rd, Hong Kong e-mail: ambekar@hknet.com Tel.: +852-256-68983, CN |
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Abstract: | Objective/methods: The metabolism of chloramphenicol succinate (CAPS) by human bone marrow was studied in vitro using 75 marrow samples. Whole
marrow samples were incubated with CAPS with or without reduced nicotinamide adenine dinucleotide phosphate for 1, 2 and 3 h
at 37 °C. Ficoll-paque-separated 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 with whole marrow from 72 donors. Its retention time (RT
10.9 min) corresponded to chloramphenicol (CAP). When CAPS was incubated with samples of whole marrow, marrow mononuclear
cells, marrow erythrocytes, marrow plasma and peripheral 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 one 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 detected when CAPS was incubated for 3 h with whole marrow from two other donors.
Conclusion: These studies demonstrated that CAPS may be metabolised to CAP and occasionally other metabolites in human bone marrow.
This novel observation is particularly important because the bone marrow is known to be a target organ for chloramphenicol
toxicity.
Received: 22 December 1999 / Accepted in revised form: 22 March 2000 |
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Keywords: | Chloramphenicol succinate Chloramphenicol Human bone marrow |
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