In vivo investigation of placental transfer early in human pregnancy.
The use of coelocentesis to study placental drug transfer in the first trimester has required the adaptation of existing pharmacologic models to the changing anatomical structures present before and after 12 weeks of gestation. The biochemical properties of the coelomic and amniotic fluids are important parameters in evaluating the pharmacokinetics of drugs and toxins in early pregnancy. In particular, the protein concentration and pH of these fluids are significantly different and vary widely with gestational age. These biochemical variations are less likely to influence the distribution of inert substances such as inulin inside the first trimester conception cavities than the distribution of drugs such as diazepam or propofol. This can explain why they are not all accumulating inside the exocoelomic cavity. It has been demonstrated that the permeability of the placenta is greater in early pregnancy than at term. Furthermore, because of the slow turn-over of the coelomic fluid, substances such as nicotine to which the mother is chronically exposed accumulate inside the exocoelomic cavity. This prolonged fetal exposure to tobacco carcinogens has important teratogenic implications and should be further explored.
Jauniaux
E
E
Academic Department of Obstetrics and Gynaecology, Royal Free and University College, London Medical School, 86-96 Chenies Mews, WC1E 6HX, London, UK. e.jauniaux@ucl.ac.uk
Gulbis
B
B
D001826:Body Fluids; D003975:Diazepam / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007444:Inulin / Q000493:pharmacokinetics; D009538:Nicotine / Q000493:pharmacokinetics; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011264:Pregnancy Trimesters; D015742:Propofol / Q000493:pharmacokinetics; D013396:Suction; D016216:Ultrasonography, Prenatal / Q000379:methods*; D015017:Yolk Sac / Q000000981:diagnostic imaging
D004364:Pharmaceutical Preparations; D009538:Nicotine; D007444:Inulin; D003975:Diazepam; D015742:Propofol