Effects of cefotaxime on the serum protein binding of sulfisoxazole.

The possible acylating effects of cefotaxime on sulfisoxazole binding to serum proteins were evaluated in vitro in samples of human sera incubated with 50-1000 micrograms ml-1 cefotaxime at 37 degrees for 1 h and then dialyzed against saline. This incubation resulted in concentration-related increases in the free fraction of sulfisoxazole (+25 per cent, +30 per cent, and +45 per cent, with 250, 500, and 1000 micrograms ml-1 cefotaxime, respectively). Sulfisoxazole binding was also studied in samples of sera from patients given prophylactic cefotaxime (3 g d-1, IV) following elective surgery. Sulfisoxazole free fraction increased from 7.6 +/- 0.7 per cent in samples obtained before starting treatment to 9.2 +/- 0.8 per cent 24 h thereafter, and to 10.4 +/- 1.0 per cent after 5 days of treatment, but this difference was not statistically significant. A Scatchard plot of pooled samples showed a reduction in overall affinity (from 2.38 X 10(-4) M to 1.77 X 10(-4) M) without changes in the number of binding sites. The effects of cefotaxime on sulfisoxazole binding and kinetics were also studied experimentally in the rabbit. Treatment with 30 mg kg-1 cefotaxime t.i.d. for 2 days increased the unbound fraction of sulfisoxazole in vivo, from 17.2 +/- 2.9 per cent to 27.3 +/- 3.6 per cent (p less than 0.02). Treatment with high doses of cefotaxime, and perhaps other 3-acetoxymethylcephalosporins, may result in changes in the serum protein binding of some acidic drugs.