Effect of norgestrel on blood-lipid constituents in relation to its biological activity

Having considered the lipophilicity of norgestrel (log p = 3.31) an important contributor to its action mechanism, interaction of the drug with total lipids of blood have been investigated using phospholipid binding, fatty acid composition and peroxidation phenomena as the parameters under investigation. The objective was to derive an insight into the pharmacodynamic behavior of the drug. Significant loss of phospholipid along with changes in fatty acid composition was observed after incubation of whole blood with norgestrel (60 ng/ml, contraceptive concentration in blood). This may be ascribed to binding affinity of norgestrel with lipid constituents in blood. Lipid binding affinity of the drug may have a role in the mediation of its therapeutic effect. Lipid peroxidation induction potential of norgestrel has been quantitatively measured in the context of its toxicity. The results reveal that norgestrel caused significant extent of lipid peroxidation. Ascorbic acid, an antioxidant, could significantly reduce norgestrel-induced lipid peroxidation.