Lorentzen H, Kallehave F, Kolmos H J, Knigge U, Bülow J, Gottrup F
Copenhagen Wound Healing Center, Bispebjerg University Hospital, Denmark.
Antimicrob Agents Chemother. 1996 Aug;40(8):1785-9. doi: 10.1128/AAC.40.8.1785.
Wound infections frequently originate from the subcutaneous tissue. The effect of gentamicin in subcutaneous tissue has, however, normally been evaluated from concentrations in blood or wound fluid. The aim of the present study was to investigate the pharmacokinetic properties of gentamicin in human subcutaneous adipose tissue by a microdialysis technique. Seven healthy young volunteers each had four microdialysis probes placed in the fat (subcutaneous) layer of the abdominal skin. After the administration of a 240-mg gentamicin intravenous bolus, consecutive measurements of the drug concentrations in serum and subcutaneous interstitial fluid were obtained simultaneously for 6 h. The tissue gentamicin concentration peaked after 10 to 30 min. The peak concentration in the tissue was 6.7 +/- 2.0 mg.liter-1 (standard deviation), equivalent to 39.1% of the peak concentration in serum. The area under the concentration-versus-time curve for the first 6 h in the tissue was 1,281 +/- 390.0) mg.min liter-1, equivalent to 59.7% of the area under the concentration-versus-time curve in serum. It is concluded that the microdialysis technique can be used to make dynamic and quantitative measurements of the gentamicin concentration in human subcutaneous tissue. In this adipose tissue, the peak concentrations of gentamicin were approximately seven times the MIC for Pseudomonas aeruginosa and 33 times the MIC for Staphylococcus aureus after the administration of an intravenous bolus of 240 mg, indicating the presence of sufficient concentrations in the adipose tissue to be effective against common bacteria.
伤口感染常常起源于皮下组织。然而,庆大霉素在皮下组织中的作用通常是根据血液或伤口渗出液中的浓度来评估的。本研究的目的是通过微透析技术研究庆大霉素在人体皮下脂肪组织中的药代动力学特性。7名健康年轻志愿者每人在腹部皮肤的脂肪(皮下)层放置4个微透析探针。静脉注射240mg庆大霉素后,同时连续6小时测定血清和皮下间质液中的药物浓度。组织中庆大霉素浓度在10至30分钟后达到峰值。组织中的峰值浓度为6.7±2.0mg·L-1(标准差),相当于血清中峰值浓度的39.1%。组织中前6小时浓度-时间曲线下面积为1281±390.0mg·min·L-1,相当于血清中浓度-时间曲线下面积的59.7%。结论是微透析技术可用于动态定量测定人体皮下组织中庆大霉素的浓度。在该脂肪组织中,静脉注射240mg后,庆大霉素的峰值浓度约为铜绿假单胞菌最低抑菌浓度的7倍,金黄色葡萄球菌最低抑菌浓度的33倍,表明脂肪组织中存在足够的浓度以有效对抗常见细菌。