Hardy M L, Hsu R C, Short C R
J Vet Pharmacol Ther. 1985 Dec;8(4):382-92. doi: 10.1111/j.1365-2885.1985.tb00971.x.
This study investigated the potential for nephrotoxicity of gentamicin in cats by measuring marker enzyme concentrations, [Na], [K], osmolality, and pH of the urine, and blood urea nitrogen (BUN) levels. Gentamicin was administered i.m. at 4.4 mg/kg once daily (s.i.d.) or twice daily (b.i.d.) for 7 days. Concentrations of lactic dehydrogenase (LDH), lysozyme (LZM), alkaline phosphatase (AP), and glutamate dehydrogenase (GD) were measured as total 24-h excretions. The s.i.d. regimen produced only a slight increase in LDH excretion after 5 days, whereas the b.i.d. regimen caused an increase in the excretion of all enzymes. The greatest elevations were observed for LZM and LDH. Of the enzymes studied, these appeared to be the most appropriate to monitor for potential nephrotoxicity, except that urinary concentrations did not correlate well with duration of gentamicin administration. Only slight elevations in BUN were observed for either regimen. Single daily administration increased urine osmolality slightly, but b.i.d. treatment caused a marked and immediate decrease in urine osmolality, [Na], and total Na excretion. Urinary [K] was also depressed, as was total K excretion after 6 days. Urine pH was not substantially affected. This study showed that the recommended daily dose of 4.4 mg/kg produced little if any evidence of nephrotoxicity as indicated by the parameters measured. Twice daily dosing, however, produced elevations in urine enzyme concentrations, and markedly decreased urine osmolality and Na and K excretion. Compared to other species studied, the cat appears particularly sensitive to urine concentrating alterations resulting from repeated gentamicin administration.
本研究通过测量标记酶浓度、尿液中的[Na]、[K]、渗透压和pH值以及血尿素氮(BUN)水平,调查庆大霉素对猫的肾毒性潜力。庆大霉素以4.4mg/kg的剂量肌肉注射,每日一次(s.i.d.)或每日两次(b.i.d.),持续7天。测量乳酸脱氢酶(LDH)、溶菌酶(LZM)、碱性磷酸酶(AP)和谷氨酸脱氢酶(GD)的浓度作为24小时总排泄量。每日一次给药方案在5天后仅使LDH排泄量略有增加,而每日两次给药方案导致所有酶的排泄量增加。LZM和LDH的升高最为明显。在所研究的酶中,这些似乎是监测潜在肾毒性最合适的指标,只是尿液浓度与庆大霉素给药持续时间的相关性不佳。两种给药方案均仅观察到BUN略有升高。每日单次给药使尿渗透压略有增加,但每日两次给药导致尿渗透压、[Na]和总钠排泄量显著且立即下降。尿[K]也降低,6天后总钾排泄量也是如此。尿液pH值未受到实质性影响。本研究表明,所测量的参数显示,推荐的每日剂量4.4mg/kg几乎没有肾毒性证据。然而,每日两次给药导致尿酶浓度升高,并显著降低尿渗透压以及钠和钾的排泄。与其他研究的物种相比,猫似乎对重复给予庆大霉素导致的尿液浓缩改变特别敏感。