The influence of renal functional changes on the intrarenal distribution and urinary kinetics of amdinocillin

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.