Drug metabolism fetal

Dr. Meskin s major areas of research interest include (1) hepatic drug metabolism and the effects of nutritional factors on drug metabolism and clearance (2) nutrient-drug interactions (3) the role of bioactive non-nutrients (phytochemicals, herbs, botanicals, and nutritional supplements) in disease prevention and health promotion (4) fetal pharmacology and fetal, maternal, and pediatric nutrition (5) nutrition education and (6) the development of educational programs for improving science literacy and combating health fraud. 

Both in vitro and in vivo metabolic studies have shown that some drug metabolism occurs or can be induced in placental tissues (20). Further degradation of parent chloroquine that reaches the placenta would result in the appearance of less chloroquine and more of the nonpolar metabolites in the fetal or neonatal circulation. (17). 

Blake MJ, Castro F, Feeder JS, Kearns GF. Ontogeny of drug metabolizing enzymes in the neonate. Semin Fetal Neonatal Med 2005 10 123-38. 

Gillette, J. R., Menard, R. H., Stripp, B. Active products of fetal drug metabolism. Clin. Pharmacol. Ther. 14, 680 (1973). 

Dotta A, Chukhlantseva N (2012) Ontogeny and drug metabolism in new borns. J Metern Fetal Neonatal Med 4 83-84... 

Age. The pharmacokinetic and pharmacodynamic effects of a drug can be influenced by age, and drug metabolism plays an important role in understanding the differences observed. Differences between the levels of metabolism enzymes for the fetal and neonatal (first 4 weeks postpartum) liver versus the adult liver have been observed in both animal and human studies (125). At birth, total CYP levels are approximately 30%of adult levels and glucuronidation activity is at 10-30% of adult levels. Interestingly, sulfotransferase activity in neonates seems to be comparable with that in adults. 

While rodents probably serve as the most utilized safety testing animal model for human health protection, there are limitations that are important to recognize. Beyond fundamental xenogenic differences with humans that can result in species differences in pharmacokinetics and actions of certain chemicals, rodent and human immune development does not proceed on an identical timeline. Landreth (2002) and Landreth and Dodson (2005) have shown that some events that occur gestationally in humans happen postnatally in rodents. This may be a consideration if limited exposure windows are utilized or if the maternally transferred exposure in rodents could not simulate the appropriate human fetal exposure. Therefore, knowledge of drug metabolism and the... 

Pelkonen, O., louppila, P, and Karki, N. (1973). Attempts to induce drug metabolism in hnman fetal liver and placenta by the administration of phenobarbital to mothers. Arch. Int. Pharmacodyn. Ther. 202, 288-297. 

---