Effect of food restriction (undernutrition) on pharmacokinetics of norethindrone in rabbits

Our previous studies have shown that the plasma norethindrone (NET) elimination is faster in women of low socio-economic group as compared to those of high socio-economic group. Undernutrition being very common in low socio-economic group, using an animal model, efforts were made to determine whether these differences were due to differences in the nutritional status of these two group of women. The experimental animals consisted of a set of twelve female rabbits, divided equally into two groups. One group (A) was fed on a stock diet ad libitum while the second group (B) received the diet in restricted amounts (half of that consumed by animals of group A). At the end of three months, radiolabelled NET was administered intravenously and plasma drug levels were determined at frequent intervals up to 24 hours. The plasma values were subjected to pharmacokinetic analysis. Food restriction to the extent of 50% resulted in a 20% deficit of body weight as compared to controls. The half-lives of alpha and beta phases were shortened in the restricted group resulting in an enhanced metabolic clearance rate of NET in this group. Though the differences were not statistically significant, the volume of distribution tended to be lower and the dose excreted in urine higher when food restriction was imposed.