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Intrarenal concentrations of ampicillin in acute pyelonephritis

The intracortical, medullary, and papillary distribution of ampicillin was studied in normal and pyelonephritic rats. At 4 days after induction of pyelonephritis, the animals were given a single injection of 100 mg of ampicillin per kg or were treated for 1 week with two daily doses of 100 mg/kg. Major differences in the intrarenal distribution of ampicillin were noted between normal and pyelonephritic animals. At 2 hours after injection, the concentrations of ampicillin in all parts of the infected kidneys were significantly lower (P less than 0.05) than in normal kidneys. The area under the curve (micrograms.minute per milliliter) over a 4-h period after single injection was much lower in the medulla (6.3 +/- 0.9) and papilla (29.6 +/- 4.2) of infected kidneys than in the medulla (11.2 +/- 1.6) and papilla (44 +/- 10.1) of noninfected kidneys. Whereas the ratio of concentration in tissue to concentration in serum ranged to 11.1 in the papilla of normal animals, this ratio was reduced to 2.4 in the presence of pyelonephritis. The diminution of the concentration gradient was also striking in the urine, where there was a reduction of more than threefold in pyelonephritic animals. One week of therapy resulted in a noticeable reduction of the inflammatory process associated with a return to near-normal intrarenal distribution of ampicillin. In normal rats treated with multiple doses, there were decreases of the antibiotic concentrations in serum and kidneys and in the area under the curve for these tissues.