Regamey C, Schaberg D, Kirby W M
Antimicrob Agents Chemother. 1972 Apr;1(4):329-32. doi: 10.1128/AAC.1.4.329.
In monitoring gentamicin concentrations in the blood of patients with renal insufficiency, the assayed antibiotic concentration was found to be lower when the sample was drawn as heparinized plasma rather than as serum. This lowering of gentamicin concentrations by heparin was studied further by adding increasing doses of heparin and various amounts of gentamicin to human serum. With a range of 2 to 100 units of heparin per ml, gentamicin concentrations in the serum were lowered by 9 to 14%; with higher heparin concentrations, an even greater and increasing inhibition was noticed, reaching 56% for 1,000 units/ml. This inhibitory effect of heparin on gentamicin was reversible by dilution, indicating that it was not due to degradation or to formation of an inactive chemical complex. Underestimation by the laboratory of gentamicin concentrations in blood is likely to be greatest with capillary tubes, with which the concentration of heparin is especially high. With clinical heparinization, the amount of active heparin in the blood does not exceed 10 units/ml and is for the most part under 3 units/ml; thus, therapeutically significant inhibition of the antibiotic is unlikely in patients receiving anticoagulation.
在监测肾功能不全患者血液中的庆大霉素浓度时,发现当样本采集为肝素化血浆而非血清时,所检测到的抗生素浓度较低。通过向人血清中添加递增剂量的肝素和不同量的庆大霉素,进一步研究了肝素对庆大霉素浓度的降低作用。每毫升血清中肝素含量在2至100单位范围内时,血清中庆大霉素浓度降低了9%至14%;肝素浓度更高时,抑制作用更明显且持续增强,1000单位/毫升时达到56%。肝素对庆大霉素的这种抑制作用可通过稀释逆转,表明其并非由于降解或形成无活性化学复合物所致。使用毛细管时,血液中肝素浓度特别高,实验室对血液中庆大霉素浓度的低估可能最为严重。在临床肝素化过程中,血液中活性肝素的量不超过10单位/毫升,且大部分低于3单位/毫升;因此,接受抗凝治疗的患者不太可能出现具有治疗意义的抗生素抑制情况。