Renal extraction of gentamicin in anesthetized dogs

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 mug/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.