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Deposition of drugs in the fetus

المؤلف:  Sue Jickells , Adam Negrusz (Editors)

المصدر:  Clarkes Analytical Forensic Toxicology

الجزء والصفحة:  258

2026-10-20

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Deposition of drugs in the fetus

Drugs and their metabolites have been detected in the urine and plasma of newborn humans and animals. However, it is difficult to determine the metabolic fate of drugs in utero. Each of the major metabolic pathways can be promoted by placental and/or fetal enzymes and although the reaction rates appear to increase with gestational age, the presence of a metabolite in the fetus does not necessarily reflect the ability of the fetus to metabolise the drug. It has been suggested that drugs reach the fetus by passive diffusion of small-molecule, lipid-soluble drugs across the placenta. The placenta was thought to be a protective barrier for the fetus, disallowing passive diffusion of drugs; however, the well documented effects of alcohol and thalidomide do not uphold this theory. The rate of drug transfer through the placenta is affected by the molecular size of the drug, the degree of ionisa tion of the drug, the hydrophobicity of the drug, blood flow to the placenta and the degree of protein binding to maternal and/or fetal plasma. The ability of the fetus to swallow amniotic fluid usually begins around the 12th week of gestation. The binding of drugs and metabolites to proteins in the amniotic fluid which is subsequently swallowed by the fetus may account for drug exposure of the fetus. Drug metabolites may be formed by the fetal liver, and excreted into the bile or urine. From the bile, they are deposited into the meconium; from the urine they are excreted into the amniotic fluid and re-circulated through fetal swallowing. Thus, meconium is a final depository for drugs to which the fetus is exposed. However, some studies concluded that fetal swallowing is not the primary mechanism by which drugs enter the fetus as was previously thought and that in fact there are other routes by which the fetus is drug exposed. Postmortem analysis of human fetuses exposed to cocaine during pregnancy revealed the presence of cocaine in the meconium of a 17-week-old fetus, implying that fetal exposure can be determined even in the case of a very premature fetus. Further, the authors claimed that the amount of cocaine found in the meconium was proportional to the amount of cocaine used by the mother during gestation. Their observations were supported by animal research.