Oie S, Levy G
J Pharm Sci. 1979 Jan;68(1):6-9. doi: 10.1002/jps.2600680106.
The effect of sulfisoxazole on the time course of free (unbound) bilirubin concentrations in plasma was studied. Normal adult rats were made hyperbilirubinemic by continuous intravenous infusion of bilirubin. Sulfisoxazole was administered by either rapid intravenous injection or slow intravenous infusion, and the plasma concentrations of free and total (free plus bound) unconjugated bilirubin were determined as a function of time. Rapid injection of sulfisoxazole caused a rapid and pronounced decrease of total bilirubin concentrations in plasma but had only a transient effect on the concentration of free bilirubin. Slow infusion of sulfisoxazole caused a gradual and eventually pronounced decrease of total bilirubin concentrations in plasma but had no apparent effect on the concentration of free bilirubin at any time. These results are consistent with recently developed pharmacokinetic theory according to which the plasma clearance of total bilirubin should increase upon administration of a displacing agent while the plasma clearance of free bilirubin should remain unchanged. Bilirubin-induced encephalopathy caused by sulfisoxazole or other displacing agents may be due to very transient elevations of free bilirubin concentrations in plasma of infants with elevated plasma concentrations of total bilirubin and the consequent redistribution of the pigment to extravascular sites, including the brain.
研究了磺胺异恶唑对血浆中游离（未结合）胆红素浓度随时间变化的影响。通过持续静脉输注胆红素使正常成年大鼠发生高胆红素血症。磺胺异恶唑通过快速静脉注射或缓慢静脉输注给药，并测定游离和总（游离加结合）未结合胆红素的血浆浓度随时间的变化。快速注射磺胺异恶唑导致血浆中总胆红素浓度迅速且显著降低，但对游离胆红素浓度仅有短暂影响。缓慢输注磺胺异恶唑导致血浆中总胆红素浓度逐渐且最终显著降低，但在任何时候对游离胆红素浓度均无明显影响。这些结果与最近发展的药代动力学理论一致，根据该理论，给予置换剂后总胆红素的血浆清除率应增加，而游离胆红素的血浆清除率应保持不变。由磺胺异恶唑或其他置换剂引起的胆红素诱导的脑病可能是由于总胆红素血浆浓度升高的婴儿血浆中游离胆红素浓度非常短暂的升高，以及随后色素重新分布到血管外部位，包括大脑。
