Effects of cefotaxime on the serum protein binding of sulfisoxazole

✍ Scribed by P. Du Souich; R. Calvo; Dr. S. Erill

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 434 KB
• Volume: 11
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510110502

✦ Synopsis

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 pg ml-l cefotaxime at 37" 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 pg ml-' cefotaxime, respectively).

Sulfisoxazole binding was also studied in samples of sera from patients given prophylactic cefotaxime (3 g d-', IV) following elective surgery. Sulfisoxazole free fraction increased from 7.6 f 0.7 per cent in samples obtained before starting treatment to 9.2 f 0.8 per cent 24 h thereafter, and to 10.4 f 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 10-4M to 1.77 X 10-4M) 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-l 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 f 3.6 per cent (u < 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.