{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T11:11:14Z","timestamp":1698145874223},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2006,1,11]],"date-time":"2006-01-11T00:00:00Z","timestamp":1136937600000},"content-version":"vor","delay-in-days":5673,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[1990,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The possible acylating effects of cefotaxime on sulfisoxazole binding to serum proteins were evaluated <jats:italic>in vitro<\/jats:italic> in samples of human sera incubated with 50\u20131000 \u03bc ml<jats:sup>\u22121<\/jats:sup> cefotaxime at 37\u00b0 for 1 h and then dialyzed against saline. This incubation resulted in concentration\u2010related increases in the free fraction of sulfisoxazole (+25 per cent, +30 per cent, and +45 per cent, with 250, 500, and 1000 \u03bc ml<jats:sup>\u22121<\/jats:sup> cefotaxime, respectively). Sulfisoxazole binding was also studied in samples of sera from patients given prophylactic cefotaxime (3 gd<jats:sup>\u22121<\/jats:sup>, IV) following elective surgery. Sulfisoxazole free fraction increased from 7\u00b76 \u00b1 0\u00b77 per cent in samples obtained before starting treatment to 9\u00b72 \u00b1 0\u00b78 per cent 24 h thereafter, and to 10\u00b74 \u00b1 1\u00b70 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\u00b738 \u00d7 10<jats:sup>\u22124<\/jats:sup>M to 1\u00b777 \u00d7 10<jats:sup>\u22124<\/jats:sup>) 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<jats:sup>\u22121<\/jats:sup> cefotaxime t.i.d. for 2 days increased the unbound fraction of sulfisoxazole <jats:italic>in vivo<\/jats:italic>, from 17\u00b72 \u00b1 2\u00b79 per cent to 27\u00b73 \u00b1 3\u00b76 per cent (<jats:italic>p<\/jats:italic> &lt; 0\u00b702). Treatment with high doses of cefotaxime, and perhaps other 3\u2010acetoxymethylcephalosporins, may result in changes in the serum protein binding of some acidic drugs.<\/jats:p>","DOI":"10.1002\/bdd.2510110502","type":"journal-article","created":{"date-parts":[[2006,10,14]],"date-time":"2006-10-14T12:13:19Z","timestamp":1160827999000},"page":"371-379","source":"Crossref","is-referenced-by-count":1,"title":["Effects of cefotaxime on the serum protein binding of sulfisoxazole"],"prefix":"10.1002","volume":"11","author":[{"given":"P. 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