Lucas D, Ménez J F, Daniel J Y, Bardou L G, Floch H H
Pharmacology. 1986;32(3):134-40. doi: 10.1159/000138162.
The in vitro effects of acetaldehyde treatment on the binding of phenytoin and diazepam to human serum albumin (HSA) and human serum proteins (HSP) have been investigated. The incorporation of acetaldehyde into proteins following incubation with different concentrations of [1,2-14 C]-acetaldehyde (0.5, 25, 100 mmol/l) was carried out. The proteins were then dialyzed so that only the stable adduct was retained. Binding of phenytoin and diazepam was then studied. Scatchard plot analysis showed a slight decrease (p less than 0.01 for HSP and 25 mmol/l acetaldehyde) in the number of binding sites for phenytoin when the acetaldehyde/protein ratio was increased. The affinity constant was also increased (p less than 0.01) with 100 mmol/l acetaldehyde. No change could be demonstrated in the number of diazepam binding sites on HSA; an increase in the binding capacity of HSP was shown following incubation with 25 mmol/l acetaldehyde. The fraction of drug bound at therapeutic levels has been also calculated for both drugs. An increase for diazepam but no change for phenytoin can be observed before or after treatment of proteins with acetaldehyde.
研究了乙醛处理对苯妥英和地西泮与人血清白蛋白（HSA）及人血清蛋白（HSP）结合的体外效应。将蛋白质与不同浓度（0.5、25、100 mmol/L）的[1,2-¹⁴C]-乙醛孵育，使乙醛掺入蛋白质中。然后对蛋白质进行透析，以便仅保留稳定的加合物。接着研究苯妥英和地西泮的结合情况。Scatchard图分析表明，当乙醛/蛋白质比例增加时，苯妥英的结合位点数略有减少（对于HSP和25 mmol/L乙醛，p小于0.01）。使用100 mmol/L乙醛时，亲和常数也增加（p小于0.01）。未发现HSA上地西泮结合位点数有变化；与25 mmol/L乙醛孵育后，HSP的结合能力有所增加。还计算了两种药物在治疗水平下的结合分数。在用乙醛处理蛋白质之前或之后，地西泮的结合分数增加，而苯妥英的结合分数无变化。
