Renal Extraction of Gentamicin in Anesthetized Dogs

Author:

Chiu Peter J. S.1,Brown Arthur1,Miller George1,Long James F.1

Affiliation:

1. Schering Corporation, Research Laboratories Division, Bloomfield, New Jersey 07003

Abstract

The tubular handling of gentamicin (G) and its intrarenal distribution were determined to elucidate the mechanism of G accumulation in the kidney. At a serum level of 11.1 ± 0.5 μg/ml (10 animals), as maintained by constant infusion for 5 h, serum Na + and K + , arterial pressure, effective renal plasma flow and glomerular filtration rate remained undisturbed. The clearance values in milliliters per minute for G, inulin, and p -aminohippuric acid were 40.3 ± 1.8, 49.9 ± 2.8, and 132 ± 14, respectively. The ratio of clearance of G to clearance of inulin was 0.82 ± 0.04 ( P < 0.005), suggesting net reabsorption of G by the renal tubules. The renal cortex/serum ratio for G was 11.9 ± 2.1, and the medulla/serum ratio was 2.7 ± 0.4, indicating greater uptake of G by the cortex. The extraction ratio of p -aminohippuric acid was 0.74 ± 0.03. In contrast, the extraction ratio of G was 0.20 ± 0.03, which was significantly lower than that of inulin (0.30 ± 0.04). It is concluded that the accumulation of G in the cortex was due to tubular reabsorption. Probably some of the reabsorbed G became trapped in the epithelial cells after crossing the luminal membrane, whereas some returned to the circulation.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference37 articles.

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2. Renal excretion of gentamicin in chronic pyelonephritis;Bergan T.;Acta Med.,1971

3. Black J. B. Calesnick D. Williams and M. J. Weinstein. 1964. Pharmacology of gentamicin a new broad-spectrum antibiotic. p. 138-152. Antimicrob. Agents Chemother. 1963.

4. Gentamicin in gram-negative urinary and pulmonary infections;Brayton R. G.;Arch. Intern. Med.,1964

5. A rapid method for the determination of para-aminohippuric acid in kidney function tests;Brun C.;J. Lab. Clin. Med.,1951

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