INTERACTION BETWEEN PROPOFOL AND SULFISOXAZOLE IN MICE AN IN-VIVO ANDIN-VITRO STUDY

The effect of sulfisoxazole on the propofol response has been investig ated in an animal model. Doses of propofol (0, 50, 75 and 100 mg/Kg in traperitoneal route) were administered to control (n=36) and sulfisoxa zole pretreated mice (n=36). The impairment of righting reflex and str uggle response were evaluated before and 5, 10, 15, 20, 30, 40, 50 and 60 minutes after propofol administration. Ten minutes after administr ation of the different doses of propofol, total plasma concentration w as measured in both groups by high performance liquid chromatography. Protein binding displacement was evaluated in vitro by the ultrafiltra tion technique. Pretreatment with sulfisoxazole produced an important enhancement in the effect of propofol in both tests. This change was r eflected in a significant increase in the area under the time-effect c urve (p<0.001) and in a shift of the log dose-effect relationship to t he left. Sufisoxazole itself did not produce any effect on either test . ED(50) for the righting reflex was significantly reduced from 114 mg /kg to 64 mg/kg in sulfisoxazole pretreated groups and it fell from 87 mg/kg to 43 mg/kg for the struggle response test. No changes in the t otal plasma concentration and protein binding were observed. On the ba sis of these results, it was concluded that a clinical interaction cou ld be expected but this cannot be explained by an alteration in the pr otein binding.