Saha A, De A U, Sengupta C
Department of Chemical Technology, University of Calcutta, 92, A P C Road, Calcutta 700 009, India.
Indian J Exp Biol. 2000 Sep;38(9):906-11.
Lipophilicity (log P) of the drug plays an important role when drug reaches in the critical reaction site, i.e., active site cum receptors where the major constituent is lipid moieties. The drug molecule may be responsible for altering the lipid constituents, which is measured in terms of phosphorus content and can be explained by their fatty acid changes that are linked with biological effect of the drug. Having considered the lipophilicity of ethinyl estradiol (log P = 3.67), its interactions with the whole lipid of goat blood have been investigated along with fatty acid changes and lipid peroxidation phenomena. There was significant loss of phosphorus content of phospholipid and change of fatty acid constituents of whole lipid. This may be ascribed to binding affinity of ethinyl estradiol with lipid constituents in blood. Lipid binding potential of the drug may have role in its therapeutic effect. The peroxidation induced by drug has been quantitatively measured along with its suppression by using antioxidant. The results reveal that ethinyl estradiol caused significant extent of lipid peroxidation. Ascorbic acid, a promising antioxidant could significantly reduce drug induced lipid peroxidation.
当药物到达关键反应部位,即主要成分是脂质部分的活性位点兼受体时,药物的亲脂性(log P)起着重要作用。药物分子可能会改变脂质成分,这可以通过磷含量来衡量,并且可以用与药物生物效应相关的脂肪酸变化来解释。考虑到乙炔雌二醇的亲脂性(log P = 3.67),研究了它与山羊血液中全脂质的相互作用以及脂肪酸变化和脂质过氧化现象。磷脂的磷含量显著降低,全脂质的脂肪酸成分发生变化。这可能归因于乙炔雌二醇与血液中脂质成分的结合亲和力。药物的脂质结合潜力可能在其治疗效果中起作用。已定量测定了药物诱导的过氧化作用以及使用抗氧化剂对其的抑制作用。结果表明,乙炔雌二醇引起了显著程度的脂质过氧化。抗坏血酸是一种有前景的抗氧化剂,它可以显著降低药物诱导的脂质过氧化。