Effect of desogestrel on blood-lipid in relation to its biological activities

Desogestrel (DG), a 19-nor progestin, is widely used in replacement therapy as a contraceptive steroidal hormone. Considering the importance of its partition coefficient parameter (log P = 5.68), a significant contributor to its action mechanism, interactions of the drug with blood-lipids had been investigated using phospholipid binding, fatty acid composition and peroxidation phenomena as the parameters under investigation to explain its pharmacodynamic behavior. From the present investigation, it was observed that lipid loss after incubation of whole blood with DG (80 ng/ml, effective contraceptive concentration in blood) for varying periods of time was accompanied with significant changes in fatty acid composition, which may be ascribed to binding affinity of DG with lipid constituents in blood that may have a role in the mediation of its therapeutic effect. Lipid peroxidation induction potential of DG has been quantitatively measured in the context of its toxicity. The results reveal that DG caused significant extent of lipid peroxidation. Ascorbic acid, an antioxidant, at equivalent human dose of 250 mg could significantly reduce DG-induced lipid peroxidation.