Accumulation of nicotine in the uterine fluid of the six-day pregnant rabbit.

In 6-day pregnant New Zealand White rabbits dosed intravenously with 3H-nicotine, the 3H-activity in the uterine fluid was approximately 5 to 11 times greater than that in the plasma at the corresponding times; 3H-nicotine itself accounted for most of this radioactivity. Dichlorodiphenyltrichloroethane (DDT) also accumulated in the uterine luminal fluid of 6-day pregnant rabbits, but to a lesser extent. However, nicotine or DDT accumulation did not occur in similarly treated, nonpregnant rabbits. The radioactivity in the uterine fluid of rabbits treated with 14C-isoniazid, salicylic acid, barbital, antipyrine, and caffeine was not different from that in the plasma (uterine fluid to plasma radioactivity ratios ranged between 0.67 and 1.85) in both 6-day pregnant and nonpregnant rabbits. No differences in regard to nicotine metabolism, volume of distribution, plasma disappearance, plasma protein binding, or urinary excretion were found between 6-day pregnant and nonpregnant rabbits. Accumulation of nicotine took place in the uterine luminal fluid of nonpregnant does pretreated with either progesterone or human chorionic gonadotropin, but did not occur in does pretreated with estrogen. It is possible that the accumulation of nicotine in uterine fluid of pregnant does and in human chorionic gonadotropin- or progesterone-pretreated nonpregnant does is due to the binding of nicotine to specific uterine fluid proteins.