Cigarette smoking is a major preventable cause of fetal death and injury, yet every year a million women in the U.S. continue to smoke during pregnancy. Many of these women would like to stop smoking, but fail cessation attempts. Nicotine in tobacco products is addictive, and this addiction is the reason that those who wish to quit are unable to do so. The most effective pharmacologic adjunct to smoking cessation therapy is nicotine replacement, including nicotine gum, transdermal nicotine patches, and nicotine nasal spray. Nicotine per se may have some adverse effects during pregnancy, but these adverse effects are likely to be much less than those induced by cigarette smoking. However, the use of nicotine replacement therapy is not currently approved for use during pregnancy. Pregnancy is known to affect the metabolism of some drugs, and may result in accelerated or depressed metabolism. Little is known of the effects of pregnancy on the metabolism of nicotine. We propose to study the metabolism of nicotine in pregnancy in women of different ethnic groups. We will use a dual stable isotope infusion technique, administering intravenous deuterium-labeled nicotine (nicotine-d2) and cotinine (cotinine-d4). Cotinine is the main proximate metabolite of nicotine. From this infusion, we can determine the metabolic and renal clearances of nicotine and cotinine, the fractional conversion of nicotine to cotinine, the pattern of urinary metabolites derived from nicotine, and can estimate the daily intake of nicotine from cigarette smoking. These parameters will be compared in the first and early second trimester vs. the third trimester vs. postpartum, with a comparison of caucasians, african- americans and hispanic pregnant smokers. The resultant data on nicotine kinetics and metabolism are necessary for implementation and optimization of nicotine replacement therapy during pregnancy (not proposed in this study). In addition, understanding changes in nicotine metabolism may clarify changes in smoking behavior and exposure to tobacco toxins during pregnancy.
| Hukkanen, Janne; Dempsey, Delia; Jacob 3rd, Peyton et al. (2005) Effect of pregnancy on a measure of FMO3 activity. Br J Clin Pharmacol 60:224-6 |
| Dempsey, Delia; Jacob 3rd, Peyton; Benowitz, Neal L (2002) Accelerated metabolism of nicotine and cotinine in pregnant smokers. J Pharmacol Exp Ther 301:594-8 |
| Dempsey, D; Jacob 3rd, P; Benowitz, N L (2000) Nicotine metabolism and elimination kinetics in newborns. Clin Pharmacol Ther 67:458-65 |
