ALTERATION IN THE PHARMACOKINETIC DISPOSITION OF CIPROFLOXACIN BY SIMULTANEOUS ADMINISTRATION OF AZLOCILLIN

Healthy subjects were given single intravenous doses of ciprofloxacin, azlocillin, and the two drugs simultaneously on separate occasions. High-pressure liquid chromatographic analysis was used to assay the concentrations of both drugs in serum and urine. Pharmacokinetic parameters were calculated by noncompartmental methods. The total body (CL), renal (CL(R)), and nonrenal (CL(NR)) clearances; steady-state volume of distribution (V(ss)); and fractional urinary excretion of ciprofloxacin were all markedly decreased with the simultaneous administration of azlocillin. The disposition of azlocillin was unchanged when it was given with ciprofloxacin to when it was given alone. The pharmacokinetic parameters (mean ± standard deviation) of ciprofloxacin given alone versus in combination with azlocillin were as follows: CL, 52.2 ± 9.2 versus 33.9 ± 6.0 liters/h (P < 0.0005); CL(R), 26.5 ± 4.8 versus 16.2 ± 4.2 liters/h (P < 0.0005); CL(NR), 25.8 ± 5.5 versus 17.7 ± 4.0 liters/h (P < 0.03); V(ss), 224 ± 30 versus 166 ± 42 liters (P < 0.01); fractional urinary excretion, 0.56 ± 0.06 versus 0.43 ± 0.04 (P < 0.002), respectively. This interaction resulted in significantly higher and more prolonged concentrations of ciprofloxacin in serum, which may be beneficial in the treatment of serious gram-negative bacterial infections, but it could also produce greater toxicity or result in more pronounced effects on oxidative drug metabolism of other medications.