Bennett W M, McDougall J, Potocnik S, Wright R D, Whitworth J A
Life Sci. 1983 Jan 17;32(3):205-12. doi: 10.1016/0024-3205(83)90032-2.
Renal handling of the aminoglycoside antibiotics gentamicin and tobramycin were studied before and after one hour of constant intravenous infusions adjusted to maintain a concentration of 15 micrograms/mL. A solitary renal autotransplant model in four conscious volume replete 40 Kg sheep was used. This unique surgical preparation allows sampling of renal arterial and renal venous blood as well as urine drained through an exteriorized parotid-ureteral fistula. This surgical preparation has considerable potential in renal pharmacology since it uses a conscious, large animal. Baseline studies in this preparation demonstrated normal, 51CrEDTA and 125 I PAH, clearances which were unaffected by the drugs. Aminoglycoside binding to pooled sheep sera was 11% at physiologic PH, calcium and magnesium concentrations. A-V difference was 1.3 +/- .3 micrograms/mL and extraction by the kidney was 9 +/- 3.2% with no differences between gentamicin and tobramycin. Clearance of gentamicin was 84% and tobramycin 86% of GFR. There was no evidence of tubular injury as evidenced by unchanged urinary beta-2 microglobulin excretion. Serum Na, K, Ca and Mg did not change over the course of the study. Both drugs caused a prompt decrease in absolute and fractional sodium excretion while only gentamicin produced a kaliuresis. Early aminoglycoside effects on electrolyte balance may be an eventual determinant of nephrotoxic potential rather than differences in renal drug handling.
在以每小时恒速静脉输注调整剂量以维持15微克/毫升浓度的情况下，对庆大霉素和妥布霉素这两种氨基糖苷类抗生素的肾脏处理情况进行了研究，输注时间为1小时，研究前后各进行一次。采用了4只体重40千克、血容量充足且清醒的绵羊的单肾自体移植模型。这种独特的手术准备方式能够采集肾动脉血、肾静脉血以及通过外部化腮腺输尿管瘘引流的尿液样本。由于使用的是清醒的大型动物，这种手术准备方式在肾脏药理学方面具有相当大的潜力。在此准备方式下进行的基线研究表明，51CrEDTA和125I PAH清除率正常，且不受药物影响。在生理pH值、钙和镁浓度条件下，氨基糖苷类药物与混合绵羊血清的结合率为11%。动静脉差值为1.3±0.3微克/毫升，肾脏的摄取率为9±3.2%，庆大霉素和妥布霉素之间无差异。庆大霉素的清除率为肾小球滤过率的84%，妥布霉素为86%。尿β-2微球蛋白排泄未发生变化，表明无肾小管损伤迹象。在研究过程中，血清钠、钾、钙和镁均未改变。两种药物均导致绝对和分数钠排泄迅速减少，而只有庆大霉素引起尿钾增多。氨基糖苷类药物对电解质平衡的早期影响可能最终决定其肾毒性潜力，而非肾脏对药物处理方式的差异。
