Brown S A, Garry F B
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station 77843.
J Vet Pharmacol Ther. 1988 Dec;11(4):330-7. doi: 10.1111/j.1365-2885.1988.tb00192.x.
Gentamicin was given to six sheep at a dosage rate of 80 mg/kg/day divided into three daily doses to cause nephrotoxicity. Peak serum gentamicin concentrations rose significantly throughout dosing (P less than 0.05), but trough serum gentamicin concentrations increased dramatically (P less than 0.01) from initial concentrations of 3.2-9.1 micrograms/ml to final trough concentrations of 31.5-195 micrograms/ml by 6-10 days on gentamicin. The serum gentamicin elimination half-life (t1/2) was doubled in each animal by approximately 6 days on therapy, with the sheep that were the most clinically affected by the nephrotoxic effects of gentamicin showing increases in t1/2 earlier than those sheep that remained less intoxicated. These changes occurred before many other clinical indicators of nephrotoxicity, with only urinary enzyme excretions preceding the changes in gentamicin elimination. Thus, alterations in the elimination of gentamicin may be one of the first clinical indicators of the occurrence of gentamicin-induced nephrotoxicity.
给六只绵羊注射庆大霉素，剂量为80毫克/千克/天，分三次注射，以造成肾毒性。在整个给药过程中，血清庆大霉素峰值浓度显著升高（P<0.05），但血清庆大霉素谷浓度从最初的3.2 - 9.1微克/毫升急剧增加（P<0.01），到使用庆大霉素6 - 10天时，最终谷浓度达到31.5 - 195微克/毫升。在治疗约6天时，每只动物的血清庆大霉素消除半衰期（t1/2）增加了一倍，受庆大霉素肾毒性影响最严重的绵羊，其t1/2升高的时间比中毒较轻的绵羊更早。这些变化发生在许多其他肾毒性临床指标之前，只有尿酶排泄先于庆大霉素消除的变化。因此，庆大霉素消除的改变可能是庆大霉素诱导肾毒性发生的最早临床指标之一。
