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氯霉素代谢的重新评估:儿童血清中代谢物的检测与定量

A reappraisal of chloramphenicol metabolism: detection and quantification of metabolites in the sera of children.

作者信息

Holt D E, Hurley R, Harvey D

机构信息

Karim Centre for Meningitis Research, RPMS Institute of Obstetrics & Gynaecology, Queen Charlotte's and Chelsea Hospital, London, UK.

出版信息

J Antimicrob Chemother. 1995 Jan;35(1):115-27. doi: 10.1093/jac/35.1.115.

DOI:10.1093/jac/35.1.115
PMID:7768759
Abstract

Seventy-four samples of serum from 27 children (age range: 26 weeks preterm to 12 y) treated with chloramphenicol for serious infections, were analyzed by high performance liquid chromatography (HPLC) for the presence of chloramphenicol metabolites. Five, including a previously unreported human metabolite--chloramphenicol aldehyde, were detected and identified by comparative HPLC, enzymic degradation or gas chromatography followed by mass spectrometry. The presence of these metabolites in the serum suggests that the biotransformation of chloramphenicol takes place by oxidation, reduction and conjugation and not by conjugation alone, as has been previously supposed. Sera from 84% of the patients contained one or more metabolites, however the presence of particular compounds did not correlate with toxicity in the four patients in whom this was observed.

摘要

对27名因严重感染而接受氯霉素治疗的儿童(年龄范围:早产26周龄至12岁)的74份血清样本,采用高效液相色谱法(HPLC)分析其中氯霉素代谢物的存在情况。通过比较HPLC、酶降解或气相色谱-质谱联用,检测并鉴定出5种代谢物,其中包括一种此前未报道的人体代谢物——氯霉素醛。血清中这些代谢物的存在表明,氯霉素的生物转化是通过氧化、还原和结合反应进行的,并非如之前所认为的仅通过结合反应进行。84%的患者血清中含有一种或多种代谢物,然而,在观察到毒性反应的4名患者中,特定化合物的存在与毒性并无关联。

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