Costela J L, Carlos R, Zamacona M K, Jiménez R, Calvo R
Department of Anaesthesia, University of Granada Hospital, Spain.
Res Commun Mol Pathol Pharmacol. 1996 Jul;93(1):89-100.
The effect of sulfisoxazole on the propofol response has been investigated in an animal model. Doses of propofol (0, 50, 75 and 100 mg/Kg intraperitoneal route) were administered to control (n = 36) and sulfisoxazole pretreated mice (n = 36). The impairment of righting reflex and struggle response were evaluated before and 5, 10, 15, 20, 30, 40, 50 and 60 minutes after propofol administration. Ten minutes after administration of the different doses of propofol, total plasma concentration was measured in both groups by high performance liquid chromatography Protein binding displacement was evaluated in vitro by the ultrafiltration technique. Pretreatment with sulfisoxazole produced an important enhancement in the effect of propofol in both tests. This change was reflected in a significant increase in the area under the time-effect curve (p < 0.001) and in a shift of the log dose-effect relationship to the left. Sulfisoxazole itself did not produce any effect on either test. ED50 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 total plasma concentration and protein binding were observed. On the basis of these results, it was concluded that a clinical interaction could be expected but this cannot be explained by an alteration in the protein binding.
已在动物模型中研究了磺胺异恶唑对丙泊酚反应的影响。向对照组（n = 36）和预先用磺胺异恶唑处理的小鼠（n = 36）腹腔注射不同剂量的丙泊酚（0、50、75和100 mg/Kg）。在注射丙泊酚前以及注射后5、10、15、20、30、40、50和60分钟评估翻正反射和挣扎反应的受损情况。在注射不同剂量的丙泊酚10分钟后，通过高效液相色谱法测量两组的血浆总浓度。通过超滤技术在体外评估蛋白质结合置换情况。在两项试验中，磺胺异恶唑预处理均使丙泊酚的作用显著增强。这种变化表现为时效曲线下面积显著增加（p < 0.001）以及对数剂量-效应关系向左移动。磺胺异恶唑本身对两项试验均未产生任何作用。在预先用磺胺异恶唑处理的组中，翻正反射的半数有效剂量（ED50）从114 mg/kg显著降低至64 mg/kg，在挣扎反应试验中，ED50从87 mg/kg降至43 mg/kg。未观察到血浆总浓度和蛋白质结合的变化。基于这些结果，得出的结论是，预计会有临床相互作用，但这无法用蛋白质结合的改变来解释。
