Disturbed intrarenal distribution of gentamicin in experimental pyelonephritis due to Escherichia coli.

The intracortical, medullary, and papillary distribution of gentamicin was studied in normal and pyelonephritic rats. The animals were evaluated from 1 hr to 365 days after the end of therapy with either a single dose or two daily injections given every 12 hr for seven days. The serum levels of gentamicin at 1 hr were significantly (P less than 0.001) higher in the pyelonephritic rats than in the normal rats after one dose (26 vs. 12 microgram/ml) and 14 doses (25.7 vs. 8.8 microgram/ml). Peak concentrations or gentamicin in all parts of infected kidneys were significantly (P less than 0.001) higher than in normal kidneys. Gentamicin was still detectable at levels of 1.2 microgram/g in the cortex of one pyelonephritic animal one year after the end of therapy, when the levels of both serum creatinine (1.1 mg/100 ml) and blood urea nitrogen (30 mg/100 ml) were much higher than at seven days after the end of therapy (0.5 and 19 mg/100 ml, respectively).