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Effects of cefotaxime on the serum protein binding of sulfisoxazole
Author(s) -
Souich P. Du,
Calvo R.,
Erill S.
Publication year - 1990
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510110502
Subject(s) - cefotaxime , sulfisoxazole , incubation , chemistry , incubation period , serum concentration , pharmacology , medicine , biochemistry , antibiotics , tetracycline
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 μ ml −1 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 μ ml −1 cefotaxime, respectively). Sulfisoxazole binding was also studied in samples of sera from patients given prophylactic cefotaxime (3 gd −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 × 10 −4 M to 1·77 × 10 −4 ) 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 < 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.