Effects of oral contraceptive norethindrone on blood-lipid and lipid peroxidation parameters.
Considering importance of the lipophilicity of norethindrone (log P=2.97), a significant contributor to its mechanism of action, interaction of the drug with total lipids of goat whole 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 by correlating biological activity with drug induced changes in lipid constituents. Significant loss in phospholipid along with changes in fatty acid cotmposition was observed after incubation of whole blood with norethindrone at 56 ng/ml (effective contraceptive concentration in blood) in varying periods of time. This may be ascribed to binding affinity of norethindrone with lipid constituents in blood. Lipid binding potential of the drug may have a role in its therapeutic effect. Lipid peroxidation induction potential of norethindrone was quantitatively measured in the context of its toxicity. The results reveal that northindrone caused significant extent of lipid peroxidation. Ascorbic acid, a promising antioxidant, at equivalent human dose levels of 250 mg and 500 mg could significantly reduce norethindrone induced lipid peroxidation.
Saha
A
A
Department of Chemical Technology, University of Calcutta, India.
Roy
K
K
De
K
K
Sengupta
C
C
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology*; D005227:Fatty Acids / Q000097:blood; D006041:Goats; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000097:blood*; D009640:Norethindrone / Q000494:pharmacology*; D010758:Phosphorus / Q000032:analysis
D003280:Contraceptives, Oral, Synthetic; D005227:Fatty Acids; D008055:Lipids; D010758:Phosphorus; D001205:Ascorbic Acid; D009640:Norethindrone