Whelton A, Spilman P S, Stout R L, Delgado F A
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Ren Fail. 1987;10(2):101-6. doi: 10.3109/08860228709056323.
The maintenance of effective therapeutic concentrations of antibiotics within the renal parenchyma is an important issue in the management of acute and chronic pyelonephritis. Available clinical data indicate that an important clinical-therapeutic correlation exists between the physiologic state of the kidney and the antibiotic concentrations that can be achieved in the medulla and papilla. Using a healthy canine model, we evaluated the influence of hydration and the state of acid-base balance upon the intrarenal distribution and urinary clearance of the semisynthetic penicillin amdinocillin. Renal physiologic activity significantly modulates the intrarenal distribution pattern of this compound. During the production of maximally acid and concentrated urine, the highest renal parenchyma levels of amdinocillin are achieved. During the latter circumstances the antibiotic undergoes distal tubular nonionic diffusion, which appears to be an important contributing factor to the high medullary and papillary concentrations of the drug. Nonetheless, at all levels of tested renal physiologic activity tissue and urine drug concentrations are adequate for the treatment of sensitive urinary pathogens.
在急性和慢性肾盂肾炎的治疗中,维持肾实质内抗生素的有效治疗浓度是一个重要问题。现有临床数据表明,肾脏的生理状态与髓质和乳头中可达到的抗生素浓度之间存在重要的临床治疗相关性。我们使用健康犬模型,评估了水合作用和酸碱平衡状态对半合成青霉素氨比西林肾内分布和尿清除率的影响。肾脏生理活性显著调节该化合物的肾内分布模式。在产生最大酸度和浓缩尿时,氨比西林在肾实质中的水平最高。在后一种情况下,抗生素会发生远端肾小管非离子扩散,这似乎是药物在髓质和乳头中高浓度的一个重要促成因素。尽管如此,在所有测试的肾脏生理活性水平下,组织和尿液中的药物浓度都足以治疗敏感的尿路病原体。