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庆大霉素复合物成分的肾毒性。

Nephrotoxicity of the constituents of the gentamicin complex.

作者信息

Kohlhepp S J, Loveless M O, Kohnen P W, Houghton D C, Bennett W M, Gilbert D N

出版信息

J Infect Dis. 1984 Apr;149(4):605-14. doi: 10.1093/infdis/149.4.605.

DOI:10.1093/infdis/149.4.605
PMID:6725992
Abstract

Commercial gentamicin C is a mixture of gentamicin C1, C1a, and C2. The nephrotoxicity of each of these constituents was compared with that of the gentamicin complex. After seven days the mean creatinine level in serum was 0.8 mg/dl in rats given C2 and 0.5 mg/dl in rats given C1, C1a, or the gentamicin complex (P less than .001). Toxicity attributable to C1a was not detected until day 14, and only minimal toxicity was noted in C1-treated rats after 21 days. Nephrotoxicity caused by the gentamicin complex was similar to that caused by C2. By a new high-pressure liquid chromatographic method, the renal concentration of C1, C1a, and C2 was quantified in rats given the gentamicin complex. The results indicated an early, preferential renal accumulation of C2. Subsequently, the C2 content of 12 commercial lots of gentamicin C was measured. The C2 concentration ranged from 12.4 to 20.1 mg/ml. In short, experimental nephrotoxicity from gentamicin C is largely the result of the C2 constituent, and the concentration of this constituent in commercial preparations of gentamicin varies by as much as 7.7 mg/dl.

摘要

市售庆大霉素C是庆大霉素C1、C1a和C2的混合物。将这些成分各自的肾毒性与庆大霉素复合物的肾毒性进行了比较。7天后,给予C2的大鼠血清肌酐平均水平为0.8mg/dl,给予C1、C1a或庆大霉素复合物的大鼠血清肌酐平均水平为0.5mg/dl(P<0.001)。直到第14天才检测到C1a所致的毒性,21天后在给予C1的大鼠中仅观察到最小程度的毒性。庆大霉素复合物引起的肾毒性与C2引起的肾毒性相似。通过一种新的高压液相色谱法,对给予庆大霉素复合物的大鼠肾中C1、C1a和C2的浓度进行了定量。结果表明C2在肾脏中早期优先蓄积。随后,测定了12个市售庆大霉素C批次的C2含量。C2浓度范围为12.4至20.1mg/ml。简而言之,庆大霉素C的实验性肾毒性主要是C2成分所致,并且该成分在庆大霉素商业制剂中的浓度差异高达7.7mg/dl。

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